Biology Notes - Biological Psychology, PDF

ALL SUMARIES 13 December 2024 23:41 LESSON 1- BIOLOGICAL PSYCHOLOGY BIOLOGICAL PSYCHOLOGY □ Definition: The study of biological mechanisms behind behavior and experience, focusing on the brain and body. □ Goal: To...

ALL SUMARIES 13 December 2024 23:41 LESSON 1- BIOLOGICAL PSYCHOLOGY BIOLOGICAL PSYCHOLOGY □ Definition: The study of biological mechanisms behind behavior and experience, focusing on the brain and body. □ Goal: To relate brain function to behavior; every action has a biological cause. MIND-BODY PROBLEM □ Historical Roots: Greek-Roman mythology linked behavior to the psyche, not the brain. □ Mentalism: The mind governs behavior, but how can a non-material entity control the body? DUALISM and DESCARTES □ Descartes: Proposed mind and body are separate but connected by the brain, with the pineal gland as the bridge. MODERN THEORIES □ Materialism: Behavior is fully explained by the nervous system, rooted in evolutionary theories by Darwin and Wallace. □ Gall's Localization: Specific brain areas control different behaviors, supported by phrenology. NERVOUS SYSTEM □ The CNS (brain and spinal cord) and PNS connect the body to the brain. OUR BRAIN □ Functions: Interprets sensory information to regulate the body and is responsible for thinking, learning, memory, and emotions. □ Brain Regions: Corpus Callosum: Connects left and right hemispheres. Cerebral Cortex: Involved in planning, reasoning, language, recognition of sounds/images, and memory. Brain Stem: Regulates heart rate, breathing, sleep cycles, and emotions. Cerebellum: Controls coordination, precision, and timing of movement. NEURONS □ Structure: Nucleus, cell body, dendrites, myelin sheath, nerve endings, axons. □ Communication: Neurons transmit signals through a combination of electrical and chemical processes. □ Action Potential: Electrical signals travel along the axon to transmit information. □ Control of Behavior: Neurons shape thoughts, feelings, and decisions, influencing responses to rewards and stimuli (conditioning). THE FIRST RECORDING OF AN ACTION POTENTIAL □ Recorded by Alan Lloyd Hodgkin and Andrew Fielding Huxley in 1939 in Plymouth. THE CELLS OF THE NERVOUS SYSTEM □ Mental experiences depend on interconnected cells in the nervous system: Neurons (electrical impulses) and Glia (support and nourishment). □ The brain contains about 100 billion neurons. SANTIAGO RAMON Y CAJAL □ In the late 1800s, Santiago Ramon y Cajal showed that neurons are separate cells and do not merge, supporting Neuron Theory: neurons are the functional units of the nervous system. THE STRUCTURE OF AN ANIMAL CELL □ Neurons contain: Membrane: Separates the inside from the outside. Nucleus: Contains chromosomes. Mitochondrion: Performs metabolic activities. Ribosomes: Synthesize new proteins. Endoplasmic Reticulum: Transports synthesized proteins THE STRUCTURE OF A NEURON □ Neurons are specialized, polarized cells that receive and transmit signals. □ They have a high metabolic rate, require oxygen and glucose, and have a specialized cytoskeleton. Neurons cannot be replaced (except by stem cells). COMPONENTS OF A NEURON □ Dendrites: Receive signals; contain synaptic receptors and dendritic spines to increase surface area. □ Soma (Cell Body): Contains nucleus, mitochondria, ribosomes, and is responsible for metabolic work. □ Axon: Transmits nerve impulses; may be covered by a myelin sheath with nodes of Ranvier. Releases chemicals at presynaptic terminals. AFFERENT, EFFERENT, AND INTRINSIC NEURONS □ Afferent Axon: Carries sensory information into the structure. □ Efferent Axon: Carries information away from the structure to muscles (motor neurons). □ Intrinsic Neurons: Dendrites and axons are contained within a single structure. VARIATIONS AMONG NEURONS □ Neurons vary in size, shape, and function. Their shape determines their connection and contribution to the nervous system. Example: Purkinje cells in the cerebellum have widely branching structures. MOTOR AND SENSORY NEURONS □ Motor Neuron: Soma in the spinal cord; receives excitation from other neurons and transmits impulses to muscles. SENSORY NEURON □ Specialized at one end to be highly sensitive to a specific type of stimulation (e.g., touch, light, sound TYPES OF GLIA TYPES OF GLIA □ Astrocytes: Synchronize axon activity by wrapping around presynaptic terminals and taking up released chemicals. □ Microglia: Remove waste, viruses, and fungi from the brain. □ Oligodendrocytes & Schwann Cells: Build the myelin sheath around axons (oligodendrocytes in the brain/spinal cord, Schwann cells in the periphery).  □ Radial Glia: Guide neuron migration and axon/dendrite growth during embryonic development; differentiate into neurons, Astrocytes, or Oligodendrocytes after development. EPENDYMAL CELLS □ Cerebrospinal Fluid (CSF): A salty solution continuously secreted by the choroid plexus in the wall of ventricles. □ CSF is produced from blood and eventually returns to the bloodstream. ASTROGLIA (Astrocytes) □ Structure: Highly branched, star-shaped, forming a network through gap junctions. □ Functions: a) Take up and release neurotransmitters at synapses. b) Provide structural support and hold neurons in place. c) Surround blood vessels, forming the blood-brain barrier, regulating material exchange between blood and brain extracellular fluid. d) Increase oxygen/glucose supply by triggering vessel dilation. e) Aid in healing by forming scars to seal off damaged areas. BLOOD BRAIN BARIER: The final layer of Protection □ Function: Isolates the brain's interstitial fluid, protecting it from toxins, pathogens, and neuroactive compounds. □ Structure: Endothelial cells form tight junctions, making the barrier selectively permeable. □ Drug Transport: Some drugs (e.g., L-dopa for Parkinson’s, antihistamines, antibiotics) must cross the barrier to act in the CNS. □ Weak Areas: The barrier is weaker in regions like the hypothalamus, hypophysis, and medulla oblongata. □ Role in Immunity: The barrier blocks harmful substances to protect neurons, as they do not regenerate. ACTIVE TRANSPORT □ Definition: A protein-mediated process that requires energy to move chemicals from the blood into the brain. □ Function: Transports glucose, hormones, amino acids, and some vitamins across the blood-brain barrier. □ Challenge: The blood-brain barrier, while protective, makes it difficult for certain drugs (e.g., chemotherapy for brain cancer) to pass. NOURISHMENNT OF VERTERBRATE NEURONS □ Glucose: Neurons rely on glucose as their primary nutrient, which is one of the few substances able to cross the blood-brain barrier. □ Oxygen: The brain consumes about 20% of the body's oxygen to function properly. SCHWANN CELLS AND OLIGODENDROCYTES □ Function: Both are myelin-forming glial cells that insulate axons and speed up electrical conduction. □ Structure: Myelin is formed by concentric layers of plasma membrane that wrap around the axon, with the cytoplasm squeezed out. □ Difference: Schwann cells myelinate axons in the peripheral nervous system, while oligodendrocytes form myelin in the central nervous system. MYELIN SHEATH □ Function: Myelin is a fatty, white substance that surrounds the axon of some nerve cells, forming an electrically insulating layer that speeds up signal transmission. □ Importance: Essential for the proper functioning of the nervous system. □ Origin: Produced by glial cells, with Schwann cells forming myelin in the peripheral nervous system and oligodendrocytes in the central nervous system. □ Myelination: The process of forming the myelin sheath is called myelination or myelinogenesis. □ Saltatory Conduction: Action potentials propagate along myelinated axons by "hopping" from one node of Ranvier (gaps between myelin sheaths) to the next, increasing conduction velocity. MICROGLIA □ Function: Involved in immune response, cleaning debris and dead cells. □ Origin: Derived from white blood cells, migrating to the CNS during development. □ Types: Ramified: Resting form. Amoeboid: Activated form, engaged in phagocytosis and inflammation. □ Abundance: Smallest and least abundant glial cells (20%). LESSON 2 - EXCITABLE CELLS EXCITABLE CELLS Excitable cells, like neurons and myocytes, change their membrane potential in response to stimulation, generating action potentials. These are transient voltage changes across the membrane, facilitated by voltage-gated ion channels. RESTING MEMBRANE POTENTIAL The resting membrane potential is the electrical charge across the cell membrane when inactive, typically -70mV. This is due to unequal ion distribution: □ Sodium and Chloride are higher outside the cell. □ Potassium and Calcium are higher inside the cell. NEURON MEMBRANE STRUCTURE The neuron membrane is a phospholipid bilayer: □ Hydrophilic heads face water outside the cell. □ Hydrophobic tails face inward, avoiding water. Ions and compounds need carrier proteins to cross the membrane. MEMBRANE PERMEABILITY Permeability to compounds depends on: □ Lipid Solubility: Lipophilic molecules pass through easily. □ Molecular Size: Larger molecules need carriers to cross. MEMBRANE TRANSPORTERS Membrane transporters are proteins that move ions and large/non-lipophilic molecules across the plasma membrane. There are two main types of channels: 1) Ligand-Gated Channels (Ionotropic Receptors) Involved in synaptic transmission. Neurotransmitters bind to these channels, opening or closing them. 2) Voltage-Gated Channels Their gating mechanism depends on membrane potential, which alters their structure. These channels are essential for generating action potentials, with sodium voltage-gated channels initiating the action potential. TYPES OF TRANSPORT □ Facilitated Diffusion (Passive Transport) Does not require energy. Molecules move from areas of high to low concentration, driven by the chemical gradient. Example: Glucose transport. □ Active Transport Requires energy (ATP) to move substances against the concentration gradient, from low to high concentration. Example: Sodium-potassium pump. CONDUCTANCE AND PERMEABILITY □ Conductance refers to how easily ions can pass through a channel. Higher permeability results in higher conductance, allowing more current of ions through the channel. □ Channels are ion-selective (e.g., for sodium, potassium, chloride, calcium). ELECTROCHEMICAL GRADIENTS □ When ions move across the membrane, they create both electrical and chemical gradients, influencing the direction of ion movement. Electrical Gradient: The difference in charge across the membrane. Chemical Gradient: The difference in ion concentration across the membrane. For example, a potassium leak channel allows potassium ions to move out of the cell, driven by the concentration gradient. This results in a more positive outside the membrane and a negative inside, creating both electrical and chemical gradients. EQUILIBRIUM POTENTIAL □ An equilibrium potential is achieved when the chemical gradient and the electrical gradient balance each other. This means the movement of ions out of the cell is countered by the movement back in, creating a stable state. Example: Potassium will move out until the electrical gradient (negative charge inside) pushes it back, creating equilibrium. RESTING MEMBRANE POTENTIAL (RMP) □ The RMP is the net result of all equilibrium potentials for different ions, weighted by their permeability. □ RMP is usually around -70mV, primarily influenced by potassium, since its permeability is the highest at rest. SODIUM-POTASSIUM PUMP □ To maintain the concentration gradients of sodium and potassium, the sodium-potassium pump actively moves sodium out and potassium in, using ATP to prevent the loss of these gradients over time. This helps sustain the resting membrane potential. NERNST EQUATION □ The Nernst Equation calculates the equilibrium potential of an ion based on its concentration gradient across the membrane. □ It assumes high permeability for the ion, meaning the ion can move freely when its channel is open. GOLDMAN-HODGKIN-KATZ (GHK) EQUATION □ The GHK equation calculates the overall membrane potential by considering the equilibrium potentials of all relevant ions and their permeabilities. □ It reduces to the Nernst equation when one ion’s permeability is dominant. ION MOVEMENT & EQUILIBRIUM □ Potassium channels alone establish the equilibrium potential for potassium. □ Introducing sodium channels causes sodium to move inside the cell due to both chemical and electrical forces, making the inside less negative. □ A new equilibrium is reached where two opposing forces balance: Potassium moves out (small force), Sodium moves in (larger force). RESTING MEMBRANE POTENTIAL & SODIUM-POTASSIUM PUMP □ The resting membrane potential is shaped by the equilibrium potentials of ions and their permeabilities, with sodium and potassium playing major roles. □ The sodium-potassium pump maintains the ionic gradients by actively pumping sodium out and potassium in, preventing the loss of concentration gradients. □ The pump is ATP-dependent and crucial for sustaining the resting membrane potential. □ The pump now changes it's / again and now can be released to the inside of the cell. ELECTROGENIC PROPERTIES OF THE NA/K PUMP AND RESTING MEMBRANE POTENTIAL Sodium-Potassium Pump (Na/K pump): □ Maintains resting membrane potential and ionic gradients crucial for action potentials. □ Moves 3 Na⁺ out and 2 K⁺ in against their gradients using ATP (active transport). □ Without ATP (e.g., cell death), the pump stops, and the membrane potential fades. Na/K Pump Mechanism: 1) 3 Na⁺ ions bind on the intracellular side. 2) ATP donates a phosphate group, changing the pump's shape and opening it to the outside, releasing 3 Na⁺ ions. 3) 2 K⁺ ions bind on the extracellular side. 4) Phosphate is released, returning the pump to its original shape, and 2 K⁺ ions are released inside. ROLE OF ION GRADIENTS AND ION CHANNELS □ Ion Channels: Selective channels allow ion flow: ◊ K⁺ channels (open at rest) → K⁺ leaks out. ◊ Na⁺ channels (mostly closed) → Small Na⁺ leaks in. These ion movements create equilibrium between chemical gradients (concentration differences) and electrical gradients (charge attraction). □ Ion Gradients: At rest: K⁺ is high inside, and Na⁺ is high outside. The Na/K pump counteracts ion leaks to maintain these gradients, especially during neuronal activity when increased Na⁺ influx occurs. RESTING MEMBRANE POTENTIAL □ At rest, the membrane potential is -70mV because: High K⁺ permeability dominates (K⁺ leak channels are open). Small Na⁺ leaks in, slightly depolarizing the membrane (-90mV → -70mV). □ Equilibrium occurs when the chemical gradient driving ions and the electrical gradient (attracting ions) balance each other. PERMEABILITY CHANGES AND ACTION POTENTIALS □ Changes in ion permeability (e.g., opening/closing ion channels) shift the membrane equilibrium and potential. □ Action Potential (AP): At rest: Dominated by K⁺ permeability. AP initiation: Na⁺ channels open → Rapid Na⁺ influx → Membrane depolarizes (inside positive, outside negative). K⁺ channels temporarily close, enhancing depolarization. □ If Na⁺ permeability becomes greater than K⁺, the membrane potential moves closer to Na⁺'s equilibrium potential. KEY POINTS: 1) Resting Potential depends mainly on K⁺ permeability (40x greater than Na⁺). 2) The Na/K pump maintains ionic gradients, ensuring a stable resting potential. 3) Ion channels allow selective permeability, balancing chemical and electrical gradients. 4) Permeability changes during AP (e.g., Na⁺ influx) shift the equilibrium and depolarize the membrane. 5) At rest: Inside = negative, K⁺ inside, Na⁺ outside. Resting potential = -70mV. ION PUMPS AND MEMBRANE POTENTIAL 1) Ion Pumps Maintain Gradients: Multiple pumps continuously use ATP to maintain ion gradients (Na⁺, K⁺, Ca²⁺) and ensure a constant membrane potential for generating action potentials (APs). 2) What Determines Membrane Potential (Em)? Concentration gradients of K⁺, Na⁺, and Ca²⁺ across the membrane. Relative permeability of the membrane to each ion, regulated by ion channels (Goldman Equation). Electrogenic ion pumps, which contribute a small negative charge like the Na⁺/K⁺ ATP pump, which maintain gradients and contribute a small negative charge to Em. Goldman Equation: The membrane potential is calculated as a sum of ion equilibrium potentials, each weighted by its relative permeability. 3) What Maintains Gradients? Ion pumps use energy to counter ion diffusion: ◊ Na⁺ and Ca²⁺ into the cell. ◊ K⁺ out of the cell. Without pumps, the cell would depolarize and lose Em. SUMMARY: Em depends on: 1) Ion concentration gradients. 2) Ion permeability (conductance). 3) Electrogenic pumps maintaining gradients and contributing to Em. CHANGES IN RESTING MEMBRANE POTENTIAL 1. DEFINITIONS: □ Resting Membrane Potential (RMP): The electrical charge difference across the membrane, inside minus outside (e.g., -70 mV). □ Depolarization: Membrane potential becomes less negative or closer to zero (e.g., -70 mV to -40 mV). □ Repolarization: Return to the resting potential (e.g., -40 mV to -70 mV). □ Hyperpolarization: Membrane potential becomes more negative (e.g., -70 mV to -90 mV). Example: If chloride channels open, Cl⁻ enters the cell → hyperpolarization. 2.RESTING POTENTIAL OF THE NEURON □ The resting potential is the polarized state of a neuron before sending a nerve impulse. □ Electrical gradient: The inside of the membrane is slightly negative relative to the outside (approx. -70 mV). □ Messages in neurons develop from disturbances in the resting potential. 3. FORCES ACTING ON SODIUM AND POTASSIUM: □ The membrane is selectively permeable to ions: Sodium (Na⁺): Channels are closed at rest. Potassium (K⁺): Channels are partially open, allowing slow K⁺ leakage. 4. ION CHANNELS AND SODIUM-POTASSIUM PUMP: □ Na⁺/K⁺ pump (protein complex): Continuously pumps 3 Na⁺ out and 2 K⁺ in, maintaining the electrical gradient. 5. ELECTRICAL AND CONCENTRATION GRADIENTS: □ Electrical Gradient: Tends to pull Na⁺ and K⁺ into the cell. □ Concentration Gradient: Difference in ion distribution. Na⁺: Pulled into the cell. K⁺: Tends to leak out, carrying positive charge. 6. RESTING MEMBRANE POTENTIAL (RMP) SUMMARY: □ RMP: The potential is negative inside and positive outside. □ Determined by: a) Unequal distribution of Na⁺, K⁺, Cl⁻ ions across the membrane. b) Electrochemical gradient: Balance of electrical and chemical gradients. c) Membrane permeability: Ions with the highest permeability (e.g., K⁺) set the RMP. □ At equilibrium: There’s a constant flow of ions with no net charge change. This is maintained by the Na⁺/K⁺ pump. Key Point: Changing ion permeability shifts the equilibrium potential: □ Increased Na⁺ permeability → Membrane potential becomes positive. □ Increased K⁺ permeability → Membrane potential becomes negative. THE ACTION POTENTIAL 1. Overview: □ An action potential (AP) is an electrical signal transmitted along a neuron’s axon, propagating like a wave. □ Speed: Ranges from 1 m/s to 100 m/s. Myelin sheath enables saltatory conduction, speeding up transmission compared to unmyelinated fibers. 2. Phases of the Action Potential: 1) Depolarization Phase (Rising Phase): A small depolarization brings the membrane potential to the threshold. At threshold, the action potential fires. The membrane potential becomes progressively less negative, reaches 0 mV, then rises to a peak of +25 to +30 mV (overshoot). 2) Repolarization Phase: The membrane potential returns from positive values back to the resting level (-70 mV). 3) Hyperpolarization Phase: The membrane potential becomes slightly more negative than the resting value before stabilizing back at resting potential. Summary of Phases: □ Depolarization → Peak → Repolarization → Hyperpolarization → Resting potential. 3. Nerve Impulse Properties: □ The AP is regenerated at points along the axon, preventing it from weakening during transmission. □ Speed of Nerve Impulses: Depends on axon myelination and diameter. Faster transmission for shorter distances: e.g., a touch on the shoulder reaches the brain faster than one on the foot. □ The nervous system adapts AP properties to meet specific needs: Touch: Small timing differences are not registered. Vision: Movements must be detected accurately. 4. Key Point: □ A stimulus is required to initiate an action potential ACTION POTENTIAL GENERATION 1. Conditions for Action Potential (AP): □ To generate an AP, the membrane potential must reach the threshold of excitation. □ The resting potential remains stable until the neuron is stimulated. 2. Key Terms: □ Hyperpolarization: An increase in polarization, making the difference between electrical charges across the membrane greater (more negative). □ Depolarization: A decrease in polarization, bringing the membrane potential closer to zero. □ Threshold of Excitation: The critical level of depolarization at which a massive depolarization (action potential) is triggered. 3. AP Threshold and Generation: □ When depolarization reaches the threshold, an action potential is generated. □ This causes: A rapid depolarization of the neuron. Transmission of nerve impulses along the axon. □ The threshold value: Varies between neurons. Is consistent for an individual neuron. □ Stimulation past the threshold always triggers a nerve impulse (action potential). THE RESTING AND ACTION POTENTIAL PHASES OF RESTING AND ACTION POTENTIAL □ At rest, voltage-gated sodium channels are closed. □ Some potassium channels remain open, causing a continuous leak of potassium. □ This potassium leak maintains the resting membrane potential at -70 mV. □ A slow depolarization brings the membrane potential to the threshold. □ At this point, voltage-gated sodium channels open. These channels are voltage-dependent, opening only when the membrane reaches the threshold. □ At the Peak: Sodium permeability is at its highest as all sodium channels are open. Sodium influx drives the membrane potential towards a positive value. □ Sodium Channel Inactivation: At the peak, voltage-gated sodium channels close (inactivate). Simultaneously, voltage-gated potassium channels open because the potential has become positive. □ Repolarization: Potassium ions move out of the cell due to electrical and concentration gradients. Potassium efflux causes the inside of the cell to become less positive and then negative, restoring the membrane potential. SUMMARY OF EVENTS 1) Resting Phase: Resting membrane potential maintained by potassium leak channels. 2) Threshold: A slow depolarization brings the membrane to the threshold, opening voltage-gated sodium channels. 3) Depolarization: Sodium influx through open sodium channels drives depolarization. 4) Peak: Sodium channels inactivate, and potassium channels open. 5) Repolarization: Potassium efflux restores the membrane potential. 6) Hyperpolarization: Potassium overshoot causes the membrane to become more negative before returning to resting values. ACTION POTENTIAL PHASES  REFRACTORY PERIODS 1. ABSOLUTE REFRACTORY PERIOD □ Definition: The period during which sodium channels are inactivated, and no action potential (AP) can be generated, regardless of the stimulus strength. □ Importance: Prevents the generation of another AP and ensures unidirectional propagation of the action potential. Key Point: An AP CANNOT be triggered during the absolute refractory period. 2. RELATIVE REFRACTORY PERIOD □ Definition: The period during which some sodium channels recover and return to an active state. □ Threshold: The threshold for generating an AP is higher, requiring a stronger-than-usual stimulus to trigger an action potential. Key Point: An AP CAN be generated during the relative refractory period, but only by a stronger stimulus. IMPORTANCE OF REFRACTORY PERIODS □ They ensure that the action potential travels in one direction along the axon. VOLTAGE-ACTIVATED CHANNELS □ Definition: Channels whose permeability depends on the voltage difference across the membrane. □ Sodium and Potassium Channels: Sodium Channels: When open, positively charged sodium ions rush into the cell, generating a nerve impulse. REFRACTORY PERIOD SUMMARY 1) Absolute Refractory Period: Membrane cannot produce an action potential (sodium channels are inactivated). 2) Relative Refractory Period: A stronger stimulus is required to trigger an action potential. VOLTAGE-ACTIVATED CHANNELS □ Membrane channels whose permeability depends on the voltage difference across the membrane. □ Includes sodium and potassium channels. □ Opening of sodium channels allows sodium ions to rush in, triggering a nerve impulse. REFRACTORY PERIODS □ After an action potential, a neuron enters a refractory period, resisting the production of another action potential. ABSOLUTE REFRACTORY PERIOD: The initial phase when the membrane cannot generate another action potential. RELATIVE REFRACTORY PERIOD: The later phase where a stronger-than-usual stimulus is required to trigger another action potential. THE MOVEMENT OF SODIUM AND POTASSIUM □ After an action potential, sodium channels close quickly. □ The neuron returns to its resting state by opening potassium channels. □ Potassium ions flow out due to the concentration gradient, carrying positive charge with them. □ The sodium-potassium pump restores the original ion distribution. □ Excessive activation of neurons (many action potentials firing) can overwhelm the sodium-potassium pump, potentially leading to neuron death, especially with drugs like MDMA. RESTORING THE SODIUM-POTASSIUM PUMP □ Restoring the sodium-potassium pump’s original ion distribution takes time. □ Rapid action potentials can cause sodium buildup within the axon, which can be toxic in cases like stroke or after using certain drugs. BLOCKING SODIUM CHANNELS □ Some drugs block sodium channels, preventing action potentials. □ Local anesthetics (e.g., Lidocaine, Novocaine, Xylocaine) block sodium channels, preventing pain sensation by stopping sensory neurons from generating action potentials. □ Tetrodotoxin (TTX), found in pufferfish, is a potent sodium channel blocker that can cause death by preventing action potentials, leading to respiratory failure due to paralysis of muscles controlled by the autonomic nervous system. The AP ORIGINATES AT AND PROPAGATES FROM THE AXON HILLOCK/ INITIAL SEGMENT □ Action potentials (APs) originate at the axon hillock and initial segment, which are rich in sodium-gated voltage channels. □ While sodium channels are also present in the body and dendrites, the AP is not generated in the dendrites due to a lower concentration of channels and different types of voltage-gated channels. □ The AP propagates along the axon, carrying information, but can also back-propagate into the cell body and dendrites, serving physiological functions. □ In sensory neurons (e.g., unipolar neurons), the AP originates at the dendrites near sensory receptors, not at the axon hillock, as the dendrites are close to the sensory receptors (e.g., on the skin). The AP in these neurons is generated at the level of the dendrites. THE ALL OR NONE LAW □ Action potentials (APs) can back-propagate into the cell body and dendrites, contributing to synaptic plasticity and Long-Term Potentiation (LTP). □ The All or None Law means an AP is either generated fully or not at all. Once triggered, it always reaches the same depolarization value and returns to resting potential. □ The amplitude and speed of the AP remain constant during propagation, as new sodium channels open sequentially. □ AP intensity and speed are consistent within a neuron but can vary between neurons due to factors like resting membrane potential and ion channel types. PROPAGATION OF AN ACTION POTENTIAL  Motor/Interneurons: AP begins at the axon hillock.  Sensory Neurons: AP generation occurs at the dendrites, closer to the receptor area.  The trigger zone is where the dendrites meet the axon.  Propagation: The AP travels down the axon. REFRACTORY PERIOD: ONE-WAY DIRECTION  During the absolute refractory period, no AP can be generated, regardless of stimulus strength.  In the relative refractory period, a strong stimulus may generate an AP but with a higher threshold.  APs cannot sum and only travel in one direction due to these refractory periods. PROPAGATION OF THE ACTION POTENTIAL (AP) □ MECHANISM: The AP triggers neighboring regions to generate their own APs, moving like a domino effect. □ WAVE-LIKE MOVEMENT: As the membrane depolarizes, it moves charges inside and outside the cell, initiating APs in adjacent areas. □ DIRECTIONALITY: APs propagate in one direction, from the trigger zone to the axon terminal, prevented from backpropagating by the refractory period. □ REFRACTORY PERIOD: After the AP, sodium channels are inactivated (absolute refractory period), preventing the generation of another AP in that area, ensuring unidirectional propagation. □ PREVENTION OF REVERSAL: The refractory period ensures APs do not propagate in reverse, maintaining efficient transmission. □ IMPORTANCE OF REFRACTORY PERIOD: It controls the rate and direction of AP movement, ensuring unidirectional travel to the axon terminal. THE MYELIN SHEATH □ FUNCTION: Myelin allows APs to jump from node to node, speeding up conduction velocity. □ SALTATORY CONDUCTION: The AP "jumps" between nodes of Ranvier, resulting in faster transmission.  □ MULTIPLE SCLEROSIS: An autoimmune disease where myelin is destroyed, leading to muscle control loss, visual impairments, and potentially death. □ MYELIN STRUCTURE: Composed of fats and proteins, myelin insulates axons and is interrupted by nodes of Ranvier. □ NODE ACTION: At each node, the AP is regenerated by ion movement, speeding the impulse. SALTATORY CONDUCTION □ SPEED: Provides rapid conduction of APs. □ ENERGY EFFICIENCY: Conserves cellular energy. LOCAL NEURONS □ AXON SIZE: Short axons, communicate with nearby neurons, and do not produce action potentials. □ GRADIENT POTENTIALS: Produce graded potentials that vary in magnitude and do not follow the all-or-none law. □ RESPONSE: Depolarize or hyperpolarize in proportion to the stimulus. □ CHALLENGE IN STUDY: Difficult to study due to their small size. □ KNOWLEDGE SOURCES: Most understanding comes from studying larger neurons. □ MYTH: Only 10% of neurons are active at a time. □ TRUTH: All of the brain is used, even when it's not performing optimally. GRADED POTENTIALS □ DEFINITION: Graded potentials are the stimuli that depolarize the membrane to the threshold for an action potential to fire. □ GENERATION: These potentials occur at the synapses, dendrites, and cell body in response to input. □ TYPES: Can be either depolarizing (+) or hyperpolarizing (-). □ AMPITUDE: Variable, depending on stimulus strength, and can decrease in amplitude as they propagate. □ TRIGGERING ACTION POTENTIAL: If graded potentials are large enough at the axon hillock, they can trigger an action potential. □ PROPAGATION: Graded potentials decrease in amplitude as they travel from the synapse to the cell body. □ SYNAPTIC INPUT: Ligand release at synaptic terminals generates graded potentials, which fade with distance. □ DIFFERENCE FROM AP: Unlike action potentials, graded potentials are not constant and can vary in both size and polarity. □ Amplitude Variation: Graded potentials change in amplitude as they propagate, unlike action potentials (AP), which maintain a constant amplitude. □ Input Dependency: Amplitude depends on the strength of the stimulus. □ Location: Occur in dendrites or the cell body and can be depolarizing (+) or hyperpolarizing (-). □ Proportionality: Amplitude is proportional to stimulus strength and distance from origin. □ Triggering Stimulus: Caused by neurotransmitter interaction with post-synaptic receptors, opening ion channels (Na+, K+, Cl-). □ Propagation: The signal propagates like a wave, diminishing in amplitude with distance. □ Threshold: If strong enough, the graded potential reaches the axon hillock’s trigger zone and can generate an action potential. GP REDUCES AMPLITUDE WITH DISTANCE □ AMPLITUDE VARIABILITY: Graded potentials change amplitude while propagating and are not constant like action potentials. □ DEPENDS ON INPUT: Amplitude varies based on the strength of the triggering stimulus. □ TYPES: Graded potentials are depolarizations (+) or hyperpolarizations (-) that occur in dendrites or the cell body. □ AMPLITUDE PROPORTIONALITY: Amplitude is proportional to the stimulus strength and the distance from its origin. □ TRIGGERING STIMULUS: Interaction between neurotransmitter and receptor (ligand-gated or GPCR) opens ion channels (Na+, K+, Cl-). □ PROPAGATION: Graded potentials propagate across the cytoplasm, reducing amplitude with distance. □ THRESHOLD REACH: If strong enough, graded potentials reach the axon hillock (initial segment with Na+ channels) and, if they reach threshold, trigger an action potential. □ AMPLITUDE DEPENDENCE: Graded potential amplitude depends on stimulus strength. GP AMPLITUDE DEPENDS on the STRENGTH of the STIMULUS TEMPORAL SUMMATIONS occurs when 2 GP from one pre-synaptic neuron occur close together in time. TEMPORAL SUMMATION □ DEFINITION: Occurs when two graded potentials from one pre-synaptic neuron happen close together in time. □ SUMMATION: Unlike action potentials, graded potentials can sum up. □ AP LIMITATION: Action potentials cannot sum due to the refractory period. □ NO SUMMATION: If two graded potentials are separated in time, they do not sum. □ SUMMATION: If stimuli are close in time, they can sum, increasing the likelihood of crossing the threshold. □ RESULT: Two small stimuli, when close in time, can sum up and trigger an action potential. SPATIAL SUMMATIONS SPATIAL SUMMATION □ DEFINITION: Occurs when multiple synapses generate graded potentials at the same time, even if each signal is weak, they can sum up. □ REFRACTORY PERIOD: Does not apply to graded potentials, as they do not rely on voltage-gated sodium channels, unlike action potentials. □ GRADIENT POTENTIALS: Represent the input to the neuron, and their strength (amplitude and number of synapses) influences whether an action potential (AP) is generated. □ INTEGRATION OF INPUTS: Neurons integrate both excitatory and inhibitory inputs, summing them to determine if the membrane will cross the threshold and generate an AP. □ STRONG INHIBITION: Can prevent action potentials, effectively silencing the neuron. □ RESULT: The generation or non-generation of an AP depends on the strength of the graded potential when it reaches the trigger zone. DEPOLARIZING (EXCITATORY) + □ Graded potentials that cause depolarization are called excitatory postsynaptic potentials (EPSP). □ These positive graded potentials are stimulatory inputs, increasing the likelihood of action potential generation. HYPERPOLARIZING (INHIBITORY) - □ Inhibitory postsynaptic potentials (IPSP) cause hyperpolarization, making the membrane potential more negative. □ This inhibits the neuron, reducing the likelihood of an action potential. INTEGRATION OF EPSP AND IPSP □ The sum of EPSPs (positive) and IPSPs (negative) determines whether the threshold for an action potential is reached. □ Inhibitory inputs can prevent action potential generation, while excitatory inputs promote it. □ The neuron integrates these inputs at the cell body and axon hillock, generating an output action potential if the threshold is crossed. OUTPUT SIGNAL □ The action potential, if generated, travels down the axon, acting as the input for the next neuron. LESSON 3- THE CONCEPT OF THE SYNAPSE THE CONCEPT OF THE SYNAPSE □ Neurons communicate via chemicals at "synapses," specialized gaps between neurons, a term coined by Charles Scott Sherrington in 1906. □ Sherrington’s discovery provided crucial functional evidence of these gaps. HISTORICAL BACKGROUND  □ Cajal's Hypothesis: Santiago Ramón y Cajal hypothesized that contact points between nerve cells, later called synapses, were key to brain information processing. □ Sherrington’s Contribution: Sherrington provided the first functional evidence of synapses, studying spinal reflexes in dogs. SHERRINGTON'S INFERENCES □ Sherrington inferred synapses through synaptic delay observed in reflexes, challenging the belief in a single neural circuit. □ Reflexes like hand withdrawal from heat were thought to involve one continuous neural pathway, but delays suggested the involvement of synaptic gaps. REFLEX ARC AND SYNAPTIC DELAY □ Reflex Arc: The spinal cord processes stimuli to generate automatic muscle responses (e.g., leg flexion reflex). □ Synaptic Delay: Reflex delays indicated the existence of synaptic gaps, not just a continuous neural pathway. EXCITATORY AND INHIBITORY RESPONSES □ Sherrington discovered that synapses could produce excitatory and inhibitory responses, showing more complex neural interactions. □ He demonstrated spatial and temporal summation: small stimuli could combine to create a stronger response, with varied outcomes based on timing and location. KEY CONCEPTS □ Synaptic Delay: The delay in communication, indicating gaps between neurons. □ Spatial/Temporal Summation: Multiple small stimuli combining to produce a stronger response. □ Excitatory and Inhibitory Responses: Synapses can elicit both types of responses, revealing diverse neural interactions. CONCLUSION □ Sherrington’s work laid the foundation for understanding how neurons communicate via synapses, forming the basis for modern neuroscience 5 ELEMENTS OF A NERVOUS REFLEX 1) SENSORY RECEPTORS Detect stimuli. 2) AFFERENT NEURAL PATHWAYS Transmit sensory information to the central nervous system (CNS). 3) CONTROL CENTERS IN THE CNS The spinal cord acts as the central integrator within the CNS. 4) EFFERENT NEURAL PATHWAYS Motor neurons transmit responses from the CNS to muscles. 5) EFFECTORS Muscles execute the response. THE RELATIONSHIP AMONG A SENSORY NEURON, INTRINSIC NEURON, AND MOTOR NEURON □ Sherrington’s dog experiments showed that stimulating one paw caused the dog to retract it due to pain while extending the other paw to maintain balance. □ Double Nature: The same stimulus produced different effects on different muscles, indicating complex circuitry. CIRCUITRY OF A REFLEX □ Sensory Neuron: The pain receptor in the skin sends a signal to the spinal cord. □ Interneurons: In the spinal cord, these neurons mediate muscle contraction and relaxation in antagonistic muscle pairs. □ Antagonistic Muscles: One contracts while the other relaxes to facilitate movement. SHERRINGTON’S OBSERVATIONS □ Reflexes are slower than axonal conduction due to synaptic gaps. □ Multiple weak stimuli at different times/locations produce a stronger reflex. □ One set of muscles contracts while another relaxes, showing excitatory and inhibitory synaptic effects. IMPORTANT POINTS ABOUT REFLEXES 1) Reflexes are slower than axonal conduction. 2) Multiple weak stimuli produce a stronger reflex than a single stimulus. 3) One set of muscles excites while another relaxes. DIFFERENCE IN THE SPEED OF CONDUCTION □ Reflex conduction is slower than action potentials due to time taken for communication between neurons, supporting the existence of synapses. SHERRINGTON’s EVIDENCE FOR SYNAPTIC DELAY SHERRINGTON’S EVIDENCE FOR SYNAPTIC DELAY □ Synaptic Delay: Sherrington’s evidence showed that increasing the number of synapses slowed down conduction. More synapses lead to slower transmission of information. TEMPORAL SUMMATION □ Sherrington observed that repeated stimuli over time could produce a stronger response, a phenomenon known as temporal summation. □ This effect would not occur if there were only a direct wire connecting the sensor to the effector (muscle). □ Temporal Summation: Repeated weak stimuli can have a cumulative effect and trigger a nerve impulse when a single stimulus is too weak. SPATIAL SUMMATION □ Sherrington found that small stimuli at different points could combine to produce a stronger reflex response, known as spatial summation. □ Spatial Summation: Synaptic input from multiple locations can trigger a nerve impulse, crucial for brain functioning. □ Each neuron receives multiple inputs, often producing synchronized responses. □ Temporal and spatial summation typically occur together, with the order of axons affecting the result. GRADIENT POTENTIAL AND SYNAPSES □ Graded Potential: Stimuli arriving at different synapses can sum up in time and space to generate an action potential (AP). □ In reflexes, weak stimuli at different skin points can converge on the same neuron, summing up to produce an output (muscle contraction or relaxation). CONCLUSION □ Through these observations, Sherrington inferred that specialized structures (synapses) were responsible for these effects. THE EFFECTS OF SUMMATION □ Post-Synaptic Neuron: The neuron has long dendrites that receive multiple synaptic inputs. □ Synaptic Inputs: Inputs from various synapses arrive sequentially along the dendrites, labeled 1st, 2nd, 3rd, and 4th. □ Summation: As the signal travels along the dendrites towards the cell body, the inputs can sum up when they arrive in sequence, leading to a cumulative effect.  Inverted Spatial Organization: If the synaptic inputs arrive in reverse order (4th, 3rd, 2nd, 1st), they no longer sum up effectively, making the stimuli less efficient.  Temporal Sequence and Spatial Organization: The sequence in which stimuli arrive and their spatial arrangement are crucial for effective summation, not just their origin or strength. EXCITATORY POSTSYNAPTIC POTENTIAL (EPSP)  Presynaptic Neuron: The neuron that delivers the synaptic transmission (before the synapse).  Postsynaptic Neuron: The neuron that receives the signal at the synapse.  EPSP: A graded potential that is depolarizing (making the membrane less negative) and excitatory, moving the membrane potential closer to the threshold for generating an action potential (AP).  Summation of EPSPs: The cumulative effect of EPSPs forms the basis for temporal and spatial summation, which can lead to the generation of an AP. INHIBITORY POSTSYNAPTIC POTENTIAL (IPSP)  IPSP: A graded potential that is hyperpolarizing (making the membrane more negative), making it less likely to fire an AP.  Integration of Signals: Both EPSPs and IPSPs sum together, determining whether the neuron will generate an action potential. CONCLUSION  The timing and spatial arrangement of synaptic inputs influence the final response of the neuron, either leading to the generation of an AP or not. ANTAGONISTIC MUSCLES AND REFLEXES □ In a reflex, when one leg retracts, other muscles relax while others extend to maintain equilibrium. □ The same stimulus can produce different effects due to the involvement of both inhibitory and excitatory synapses. INHIBITORY SYNAPSES □ Sherrington observed that when a dog's leg was pinched, the retracted leg’s flexor muscles were excited, while the other three legs' muscles were inhibited. □ This suggests that an interneuron in the spinal cord sends excitatory signals to one leg's flexor muscles and inhibitory signals to the others. INHIBITORY POSTSYNAPTIC POTENTIAL (IPSP) □ IPSPs are inhibitory and act as a "brake," hyperpolarizing the membrane (making it more negative) and suppressing excitation. □ IPSPs can counteract excitatory postsynaptic potentials (EPSPs), preventing action potentials (APs) when summed together. □ IPSPs occur when synaptic input opens channels for potassium ions to exit or chloride ions to enter, hyperpolarizing the neuron and suppressing activity. EXCITATORY AND INHIBITORY SYNAPTIC INTERACTIONS □ Excitatory Synapses (EPSPs): Depolarize the membrane and bring the neuron closer to firing an AP. □ Inhibitory Synapses (IPSPs): Hyperpolarize the membrane and make it less likely to fire an AP. □ The combination of EPSPs and IPSPs integrates all stimuli and determines the final output (whether an AP occurs or not). FEEDBACK MECHANISMS IN PAIN RESPONSE □ A sensory neuron activated by pain excites the main neuron while also activating an interneuron that inhibits the main neuron after a brief delay. □ This feedback mechanism reduces the pain signal over time, providing a form of negative feedback that regulates neuronal activity. SPONTANEOUS FIRING RATE AND SYNAPTIC INPUTS □ Spontaneous Firing Rate: Postsynaptic neurons typically fire a sequence of APs, not just one. □ EPSPs increase the firing rate by depolarizing the neuron, while IPSPs decrease it by hyperpolarizing the neuron. □ Firing Modulation: The ongoing production of APs is modulated by the balance of EPSPs and IPSPs, affecting the neuron’s activity level and response. CONCLUSION □ Neurons modulate their firing rate based on the balance between excitatory and inhibitory synapses, controlling the intensity and timing of their responses. VARIETIES OF SYNAPSES □ Dendro-dendritic: A rare type where synapses occur between two dendritic branches; lacks the typical structure of a synapse. □ Axo-dendritic: The most common form, where the axon terminal of a presynaptic neuron forms a synapse with the dendrite of a postsynaptic neuron. □ Axo-extracellular: In this type, the axon terminal releases neurotransmitters into the extracellular space, influencing neighboring neurons with a modulatory effect. □ Axo-somatic: The axon terminal forms a synaptic connection with the cell body (soma) of the postsynaptic neuron. □ Axo-synaptic: A terminal synapse that connects with the presynaptic terminal of another neuron, not directly with the main cell body. □ Axo-axonic: A synapse formed directly between two axons. □ Axo-secretory: Neurons that release neurohormones into the bloodstream for hormonal signaling. Relationship Among EPSP, IPSP, and Action Potentials RELATIONSHIP AMONG EPSP, IPSP, AND ACTION POTENTIALS □ Sherrington theorized that synapses produce both "on" and "off" responses. □ The duration and effect of synapses can vary significantly. When two synapses activate simultaneously, their combined effect may be more or less than the sum of individual effects. □ Synaptic release is influenced by the arrival of the action potential at the terminal, along with background activity (constant neurotransmitter release, creating miniature potentials). TYPES OF SYNAPSES □ Chemical Synapse: Characterized by neurotransmitters. Information is transmitted chemically from the presynaptic to postsynaptic terminal. Release of neurotransmitter depends on the action potential arriving at the terminal. □ Electrical Synapse: Involves current flow through gap junctions. ELECTRICAL SYNAPSES □ Formed by gap junctions, which are channels between the presynaptic and postsynaptic terminals, allowing the action potential (AP) or graded potential (GP) to propagate through the gaps. □ Faster than chemical synapses due to the direct electrical connection between neurons, creating a continuous wiring. □ Involves depolarization with little delay, making the two neurons act as one. □ Used in special-purpose synapses for rapid transmission, such as synchronizing neuron firing. GAP JUNCTIONS □ Made of protein units (connexins) that form channels allowing ions to flow between neurons, causing depolarization and initiating an AP in the following neuron. □ The transfer of charge is much faster than neurotransmitter release in chemical synapses. □ Useful in situations requiring fast signal conduction (e.g., synchronizing heart muscle cells, certain brain regions). CHEMICAL SYNAPSES □ Use neurotransmitters to transfer signals between neurons. □ Most synapses in the nervous system are chemical. □ Signals across synapses can be excitatory or inhibitory, depending on the neurotransmitter and receptor type. ‘ANATOMY’ OF THE CHEMICAL SYNAPSE □ Pre-synaptic terminal: The part of the neuron where neurotransmitters are stored and released. □ Pre-synaptic membrane: The membrane of the pre-synaptic terminal. □ Synaptic cleft: The narrow space between the pre-synaptic and post-synaptic terminals where neurotransmitters are released. □ Post-synaptic membrane: The membrane of the post-synaptic neuron or dendritic spine where neurotransmitter binding occurs. □ Post-synaptic receptors: Specialized proteins on the post-synaptic membrane that interact with neurotransmitters, causing a response (e.g., excitatory or inhibitory post-synaptic potential). □ Neurotransmitter-receptor interaction: Each neurotransmitter has its own receptors, with several subtypes for each neurotransmitter. □ Storage granules and synaptic vesicles: Vesicles store neurotransmitters and move towards the pre-synaptic membrane to release them. □ Calcium: Triggers the release of neurotransmitters by causing vesicles to fuse with the pre-synaptic membrane. □ Mitochondria: Provide energy (ATP) for active processes involved in neurotransmitter release. □ Microtubules: Transport vesicles containing neurotransmitters from the cell body to the synapse through active transport. TRIPARTITE SYNAPSES □ Tripartite synapses: These synapses consist of three components: a) Presynaptic terminal b) Post-synaptic terminal c) Astrocytes – glial cells that play an active role in synaptic function. ASTROCYTES Astrocytes surround the synapse and help modulate synaptic activity. They buffer the neurotransmitter release, absorbing excess neurotransmitter to reduce concentration in the synaptic cleft. Function: After absorbing neurotransmitters, astrocytes generate a signal inside (often involving calcium ions), triggering the release of glial transmitters. □ Glial transmitters: These neurotransmitters modulate the activity of both the presynaptic and postsynaptic terminals, either increasing or decreasing their excitability, thus modulating synaptic communication. □ Types of neurotransmitters affected: Glutamate: Common in excitatory synapses, often modulated by astrocytes. GABA: An inhibitory neurotransmitter also modulated by astrocytes. □ Plasticity: Astrocytes are involved in synaptic plasticity, which influences long-term changes in synaptic strength. Long-Term Potentiation (LTP): A stronger response after repeated activation of a synapse. Long-Term Depression (LTD): A weaker response after repeated activation. These processes contribute to memory, learning, and perception as the brain adapts and changes based on experiences. □ Astrocyte excitability: Astrocytes can change their excitability by varying the Ca²⁺ concentration within their cytoplasm. This modulation affects the release of gliotransmitters, including: ◊ Glutamate ◊ GABA ◊ ATP/Adenosine ◊ d-Serine ◊ TNFα (Tumor Necrosis Factor alpha) “QUAD-PARTITE" SYNAPSES AND DEPRESSION QUAD-PARTITE SYNAPSES: THESE INVOLVE FOUR COMPONENTS: 1) Presynaptic terminal 2) Postsynaptic terminal 3) Astrocytes 4) Microglia – additional glial cells that modulate synaptic activity. ASTROCYTES’ ROLE: □ Buffering and Modulating: Astrocytes buffer glutamate and potassium ions in the synapse, influencing synaptic plasticity (changes in receptor expression and excitability). □ Plasticity: They regulate glutamate levels and can alter synaptic potassium levels, affecting membrane potential and neuronal excitability. □ Calcium and Glial Transmitters: Astrocytes regulate calcium and release glial transmitters to modulate the pre and postsynaptic terminals. These transmitters can increase or decrease neuronal excitability. MICROGLIA’S ROLE: □ Activity Modulation: Microglia monitor and regulate synaptic activity, especially when synapses become excessively activated, preventing overstimulation and maintaining proper plasticity. □ Pro-inflammatory State: In dysfunction, microglia can become pro-inflammatory, impairing normal plasticity mechanisms (long-term potentiation and depression), which is linked to depression. DEPRESSION AND SYNAPTIC DYSFUNCTION: □ Glial Dysfunction in Depression: Altered astrocyte and microglia activity is linked to depressive symptoms, especially those resistant to traditional drugs. □ Ketamine: Ketamine, a glutamatergic drug, has rapid antidepressant effects by influencing glutamate signaling through the prefrontal cortex and microglia. Unlike traditional antidepressants, it works within hours by restoring proper synaptic plasticity and addressing microglial dysfunction. PLASTICITY MECHANISMS: □ Aberrant Plasticity: Depression is associated with impaired synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), affecting learning and memory. These processes regulate how synapses respond to stimuli. □ Excitability Changes: Dysfunctional glial cells alter synaptic excitability, leading to aberrant plasticity and potentially contributing to mood disorders. DRUG EFFECTS: □ Ketamine: Ketamine blocks glutamate receptors (NMDA), reducing excitability and improving depression symptoms by restoring normal synaptic plasticity, particularly in the prefrontal cortex. □ Nicotine: Nicotine mimics acetylcholine by acting as an agonist on nicotinic receptors, influencing various physiological processes. SUMMARY: Astrocytes and microglia play a vital role in regulating synaptic activity and plasticity through their effects on glutamate, potassium, and calcium levels. Dysregulation of these glial cells contributes to mood disorders like depression, and treatments like ketamine work by restoring normal glutamate signaling and microglial function. These mechanisms involve complex communication between glial cells and neurons, influencing synaptic excitability, plasticity, and ultimately, brain function. NEUROTRANSMISSION IN 5 STEPS ANTEROGRADE SYNAPTIC TRANSMISSION occurs from the PRE synaptic terminal to the POST synaptic neuron. RETROGRADE transmission (e.g., ENDOCANNABINOIDS) can occur from the POST synaptic neuron to the PRE synaptic terminal. 5 STEP PROCESS OF ANTEROGRADE SYNAPTIC TRANSMISSION: 1) SYNTHESIS: The neurotransmitter is synthesized either at the axon terminal (small neurotransmitters, e.g., amino acids) or in the cell body (larger neurotransmitters) requiring gene activation and enzyme synthesis. 2) PACKAGING AND STORAGE: The neurotransmitter is packaged into vesicles in the axon terminal. 3) TRANSPORT AND RELEASE: The neurotransmitter is transported to the PRE synaptic membrane and released into the synaptic cleft when an AP arrives, triggering voltage-gated calcium channels to open, allowing Ca2+ entry. This influx triggers vesicle fusion and exocytosis. 4) RECEPTOR BINDING AND ACTIVATION: The neurotransmitter binds to POST synaptic receptors, initiating a response, such as a graded potential (EPSP or IPSP). IONOTROPIC receptors mediate fast transmission, while METABOTROPIC receptors induce slower responses via secondary messengers. 5) SIGNAL TERMINATION: The neurotransmitter is degraded or taken back into the PRE synaptic terminal to stop continued receptor activation. SYNTHESIS AND TRANSPORT DETAILS: □ Small neurotransmitters are synthesized in the axon terminal from dietary amino acids. □ Larger neurotransmitters are synthesized in the cell body, transported to the axon terminal via microtubules. NEUROTRANSMITTER RELEASE: □ AP arrival triggers voltage-gated calcium channels, allowing Ca2+ influx, which facilitates vesicle fusion and neurotransmitter release via exocytosis. RECEPTOR-SITE ACTIVATION: □ Neurotransmitters activate POST synaptic receptors, inducing EPSP (depolarization) or IPSP (hyperpolarization). □ IONOTROPIC receptors cause fast responses, while METABOTROPIC receptors cause slower, more complex reactions influencing synaptic plasticity. SIGNAL TERMINATION: □ Neurotransmitter removal is essential to prevent prolonged receptor activation, achieved via degradation or reuptake. EFFECT OF NEUROTRANSMITTER-RECEPTOR INTERACTION: When a neurotransmitter binds to its receptor, two types of graded potential deformation can occur: 1) Fast Graded Potential: Depolarizes the membrane, inducing an Excitatory Post Synaptic Potential (EPSP). Hyperpolarizes the membrane, inducing an Inhibitory Post Synaptic Potential (IPSP). These effects are mediated by IONOTROPIC RECEPTORS, which are ion channels responsible for fast transmission. 2) Slow Graded Potential: Involves a cascade of reactions that result in a change in the membrane potential, not necessarily a graded potential, or synthesis of new proteins. This is one mechanism of synaptic plasticity. Mediated by METABOTROPIC RECEPTORS, responsible for slow transmission. POST-SYNAPTIC EFFECTS: □ EPSP: Depolarizes the postsynaptic membrane, causing an excitatory action on the postsynaptic neuron. □ IPSP: Hyperpolarizes the postsynaptic membrane, causing an inhibitory action on the postsynaptic neuron. □ May also initiate other chemical reactions that modulate the excitatory or inhibitory effects or influence other functions of the receiving neuron. ADDITIONAL RECEPTOR INTERACTIONS: □ Neurotransmitter may interact with receptors on the presynaptic membrane. □ Autoreceptor: A self-receptor on the presynaptic membrane that responds to the neurotransmitter the neuron releases. □ IONOTROPIC RECEPTORS: Mediate fast transmission. □ METABOTROPIC RECEPTORS: Mediate slow transmission. EXAMPLE OF A POST-SYNAPTIC NEURON/DENDRITIC SPINE: □ Two presynaptic terminals (axons):  One releases GLUTAMATE (GLU). One releases SEROTONIN (5-HT). This example shows how different types of receptors exist for the same neurotransmitter. GLUTAMATE: □ Activates AMPA and NMDA receptors. □ These are IONOTROPIC RECEPTORS (fast activation). SEROTONIN: □ Activates METABOTROPIC RECEPTORS (slow activation). DIFFERENCE: □ Left side: Fast excitatory communication mediated by ionotropic receptors. □ Right side: Slow transmission with modulatory effects mediated by metabotropic receptors. PRE-SYNAPTIC RECEPTORS: □ Some receptors are also found on the presynaptic membrane. These presynaptic receptors can influence both postsynaptic and presynaptic neurons. □ Example: GLUTAMATE (left synapse): Receptors on presynaptic terminals modulate the system, similar to astrocytes. SEROTONIN (right synapse): Autoreceptors on the presynaptic terminal influence its own neurotransmitter release. AUTORECEPTORS: □ Located on the same presynaptic terminal. □ Regulate neurotransmitter release through feedback: Example: Dopaminergic neurons can inhibit their own release of dopamine via autoreceptors, serving as a feedback mechanism to control activity. HETERORECEPTORS: □ Located on the postsynaptic membrane or another synapse. □ Affect a different synapse or system. FEEDBACK MECHANISMS: □ Autoreceptors: Regulate the activity of the same neuron that releases the neurotransmitter (self-regulation). □ Heteroreceptors: Located on different neurons, responding to neurotransmitters from other neurons and affecting the neuron’s activity. THE QUANTUM LEAP: □ Neurotransmitter release: Measured by B. Katz via postsynaptic potential recordings. Focused on miniature potentials: spontaneous events without an AP at the presynaptic terminal. □ Observation: Miniature potentials occurred as multiples of the smallest (e.g., 1, 2, 3, 4), suggesting each corresponds to one vesicle release. □ Quantal Release: Quantum = release of one vesicle of neurotransmitter. Number of quanta required for postsynaptic response depends on Ca2+ influx into the presynaptic terminal. □ Calcium's Role: More Ca2+ results in more quanta/vesicles released. If vesicle storage is depleted, signals arrive but no neurotransmitter release occurs. Small quanta can't induce an AP. SUMMARY: □ Spontaneous activity = vesicle release, leading to "quantal release". □ Release occurs in discrete amounts: 1 quantum = 1 vesicle, 2 quanta = 2 vesicles. □ B. Katz's findings: Recorded miniature potentials, revealing quanta released in multiples to generate an AP. QUANTAL RELEASE DEPENDS ON: 1) Ca2+ entry from AP. 2) Number of vesicles docked at membrane. STEP 5: NEUROTRANSMITTER INACTIVATION Neurotransmitter inactivation is essential to terminate signaling and stop receptor activation. This can occur through: 1) DIFFUSION: Neurotransmitter diffuses away from the synaptic cleft, no longer available to bind receptors. 2) DEGRADATION: Enzymes in the synaptic cleft or presynaptic terminals break down neurotransmitters, altering their structure. 3) REUPTAKE: Specialized proteins on the presynaptic membrane reabsorb neurotransmitters from the synaptic cleft. The neurotransmitter is either degraded or recycled into another vesicle. 4) ASTROCYTE UPTAKE: Nearby astrocytes absorb neurotransmitters, storing them for later re-export to the axon terminal. INACTIVATION AND REUPTAKE OF NEUROTRANSMITTERS: □ Neurotransmitters do not stay in the synapse; they undergo inactivation or reuptake. □ During reuptake, the presynaptic neuron absorbs the neurotransmitters intact for reuse. □ Transporters are membrane proteins that facilitate this process. Examples: □ Serotonin (SERT): The serotonin transporter (SERT) on the presynaptic terminal reabsorbs serotonin. □ Acetylcholine: In the synaptic cleft, acetylcholinesterase breaks down acetylcholine into acetate and choline, which are recycled. □ Dopamine: Specific enzymes in the synaptic cleft and presynaptic terminal, along with dopamine transporters, degrade and recycle dopamine. This inactivation and recycling process ensures proper neurotransmission control. 2 DIFFERENT EZYMES OF DOPAMINE: Excess dopamine is converted into inactive chemicals by two enzymes: 1) MONOAMINE OXIDASE (MAO) 2) CATECHOL-O-METHYLTRANSFERASE (COMT) These enzymes degrade dopamine into HVA (homo-vanillic acid), an inactive chemical. This process is how dopamine is broken down. STIMULANT DRUGS Stimulant drugs like COCAINE enhance neurotransmitter activity: □ COCAINE blocks dopamine reuptake from the synaptic cleft, leading to an increased and prolonged dopamine concentration and signaling. Note: Not necessary for the exam: □ AMPHETAMINE competes with dopamine for transporters, resulting in less dopamine reuptake. It also releases dopamine from storage, which is destroyed, causing a massive increase of dopamine in the synaptic cleft. Examples of stimulant drugs affecting dopamine neurotransmission: 1) AMPHETAMINE and COCAINE stimulate dopamine synapses by increasing dopamine release from the presynaptic terminal. 2) METHYLPHENIDATE (Ritalin) blocks dopamine reuptake more gradually and is used to treat ADD. Its long-term effects on drug abuse risk are unclear. NEGATIVE FEEDBACK IN THE BRAIN: 1) Autoreceptors: Detect neurotransmitter levels and inhibit further release (feedback mechanism). 2) Postsynaptic Neurons: Release chemicals that inhibit further neurotransmitter release from the presynaptic terminal. CANNABINOIDS Cannabinoids, found in marijuana, are part of the endogenous cannabinoid system, with key neurotransmitters: □ Anandamide □ 2-AG (Acylglycerol) These bind to cannabinoid receptors 1 and 2, where THC also attaches. Endocannabinoid System: Endocannabinoids use retrograde signaling, acting as a feedback mechanism. After strong synaptic activation, postsynaptic neurons release endocannabinoids, which bind to presynaptic cannabinoid receptors, inhibiting neurotransmitter release. This activation-induced inhibition regulates neuronal activity via autostatic feedback. ENDOCANNABINOIDS: □ Lipids derived from phospholipids or cholesterol, easily passing through membranes and dissolving in oils. □ Retrograde transmission across the synapse. In marijuana, chemicals bind to anandamide or 2-AG receptors on presynaptic neurons or GABA, reducing neurotransmitter release and decreasing excitatory and inhibitory messages. EFFECTS OF SOME DRUGS AT DOPAMINE SYNAPSES NEUROTRANSMITTERS- CLASSES OF NEUROTRANSMITTERS 1) Amino Acids: Glutamate, GABA, glycine, aspartate, and others. 2) Modified Amino Acids: Acetylcholine. 3) Monoamines: Indoleamines: Serotonin. Catecholamines: Dopamine, norepinephrine, epinephrine.  4) Neuropeptides: Endorphins, substance P, neuropeptide Y, orexin, and others. 5) Purines: ATP, adenosine, and others. 6) Gases: Nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S). 7) Fatty Acids: Anandamide, 2-AG. 1) Amino Acids: Glutamate, aspartate, serine, GABA, glycine. 2) Monoamines: Dopamine, norepinephrine, epinephrine, serotonin, melatonin. 3) Others: Acetylcholine (ACh), adenosine, anandamide, histamine. 4) Peptides: Endogenous opioids, polypeptides. 5) Gases: Nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S). 6) Nucleosides: ATP, adenosine; Endocannabinoids: Anandamide (AEA), 2-AG. □ Neurons synthesize neurotransmitters from dietary substances. Acetylcholine is made from choline in milk, eggs, and nuts. Tryptophan is a precursor for serotonin. □ Catecholamines (epinephrine, norepinephrine, dopamine) contain a catechol group and an amine group. PATHWAYS IN THE SYNTHESIS OF TRANSMITTERS □ Tryptophan and Phenylalanine are precursors for neurotransmitters (e.g., dopamine) and are essential amino acids acquired from the diet. □ Lack of Tryptophan leads to lower serotonin levels. NEUROPEPTIDES □ Metabotropic Effects: Utilize various neurotransmitters. □ Neuropeptides as Neuromodulators: Require repeated stimulation for release. Trigger other neurons to release the same neuropeptide. Diffuse widely and affect many neurons via metabotropic receptors. DISTINCTIVE FEATURES OF NEUROPEPTIDES □ Synthesis: Neuropeptides synthesized in the cell body. Other neurotransmitters synthesized in the presynaptic terminal. □ Release: Neuropeptides are released from dendrites, cell body, and sides of the axon. Other neurotransmitters are released from the axon terminal. □ Release Trigger: Neuropeptides are released by repeated depolarization. Other neurotransmitters are released by a single action potential. □ Effect Spread: Neuropeptides diffuse widely and affect many neurons. Other neurotransmitters primarily affect receptors of adjacent postsynaptic cells. □ Duration of Effects: Neuropeptides have effects lasting many minutes. Other neurotransmitters have effects lasting less than a second to a few seconds. LIPID TRANSMITTERS □ Endocannabinoids: Lipid-based, synthesized from membrane phospholipids or cholesterol. Easily pass through membranes and dissolve in oils. Main examples: Anandamide and 2-AG (2-arachidonoylglycerol). Derived from arachidonic acid (unsaturated fatty acid). Bind to CB1 and CB2 receptors. Act on presynaptic receptors. GASEOUS AND ION TRANSMITTERS □ Gaseous Transmitters: Not stored in vesicles; synthesized as needed. Easily cross the cell membrane. □ Ion Transmitters: Zinc (Zn2+) is classified as a transmitter. Actively transported and packaged into vesicles, often with another transmitter (e.g., glutamate). Released into the synaptic cleft. ACTIVATING RECEPTORS OF THE POST-SYNAPTIC CELL □ Effect of Neurotransmitters: Depends on the type of receptor on the postsynaptic neuron. Same neurotransmitter can be excitatory or inhibitory based on receptor type. POST-SYNAPTIC EFFECTS □ Fast Transmission (a few milliseconds): Ionotropic receptors (ligand-regulated channels). □ Slow Transmission (tenths of seconds to hours): Metabotropic receptors. □ Very Slow Transmission (days to years). MEMBRANE CHANNELS □ Passive (Leak) Channels. □ Active (Gated) Channels: Chemically regulated. Voltage-regulated. Mechanically regulated. METABOTROPIC AND IONOTROPIC RECEPTORS  IONOTROPIC AND METABOTROPIC RECEPTORS □ Ionotropic Receptors: Function: Allow ion passage via ligand-gated ion channels. Mechanism: Neurotransmitter binds to receptor, opening the channel for ion flow (e.g., EPSP generation). Speed: Fast response (milliseconds). Structure: Composed of 5 subunits that form a pore. □ Metabotropic Receptors: Function: Not channels, but activate G-protein-coupled receptors (GPCRs) that open other channels or initiate cellular processes. Mechanism: Neurotransmitter binds, activating a G-protein (GDP-bound), which activates enzymes or generates second messengers. Effects: Can open channels or influence gene expression (e.g., receptor movement, new receptor formation). Speed: Slow response, longer processes (compared to ionotropic receptors). Impact: Modulates communication efficiency (e.g., by altering membrane polarization). SUMMARY OF METABOTROPIC RECEPTORS: □ Ion Entrance → Depolarization □ Receptor Activation → G-protein Activation □ G-protein Activation → Enzyme Activation → Second Messenger Generation □ Second Messenger → Channel Opening or Gene Expression Modulation □ Long-term Effects: Changes in membrane polarization or gene expression efficiency. NEUROTRANSMITTER EFFECTS: □ Same neurotransmitter can activate ionotropic (EPSP/IPSP) or metabotropic (second messenger pathways) receptors for varying effects. cAMP AS A SECOND MESSENGER – MODULATION □ Mechanism: Metabotropic receptor activates G-protein. G-protein subunit activates Adenylate Cyclase, converting ATP to cAMP (second messenger). cAMP activates proteins that regulate ion channels (e.g., potassium channels). □ Effects on Membrane Potential: Opening potassium channel → Hyperpolarization (more negative). Closing potassium channel → Depolarization (more positive). Changes membrane potential, modulating cell excitability. MODULATION: DEPENDING ON THE G PROTEIN, THE SAME NEUROTRANSMITTERS CAN ELICIT DIFFERENT RESPONSES  MODULATION: □ Ionotropic receptors: Fast response (direct ion channel opening). □ Metabotropic receptors: Slow response (via second messengers like cAMP). □ G-protein differences: Same neurotransmitter can cause different effects depending on the G-protein type (e.g., Gi - inhibitory, GS - stimulatory).  AMPLIFICATION: □ Second messenger (cAMP) amplifies the signal, creating a multiplier effect.  EXAMPLE WITH NOREPINEPHRINE/EPINEPHRINE: □ Alpha receptor (Gi): Reduces excitability. □ Beta receptor (GS): Increases excitability. IONOTROPIC EFFECTS:  Quick response: Neurotransmitter opens ion channels, with effects often within milliseconds.  Short-lasting: Typically rely on glutamate or GABA. THE ACETYLCHOLINE RECEPTOR (IONOTROPIC) □ Nicotinic Receptor: Closed state: The receptor forms a small internal pore. Open state: When the neurotransmitter (ligand) binds, the receptor opens, creating a larger channel for ion flow. METABOTROPIC EFFECTS & SECOND MESSENGER SYSTEMS □ Mechanism: Neurotransmitters bind to metabotropic receptors, triggering slower, longer-lasting metabolic reactions. Common neurotransmitters: dopamine, norepinephrine, serotonin, sometimes glutamate and GABA. Binding causes the receptor protein to bend, activating intracellular molecules. □ Effects: Modulates processes like taste, smell, and pain perception. SEQUENCE OF EVENTS AT A METABOTROPIC SYNAPSE 1) Neurotransmitter binds to the metabotropic receptor. 2) This induces a change in the receptor, activating the G-protein. 3) The G-protein triggers intracellular signaling, often via a second messenger. G-PROTEINS  Definition: G-proteins are coupled with GTP (guanosine triphosphate), an energy-storing molecule.  Activation: When activated, G-proteins convert from GDP (diphosphate) to GTP (triphosphate).  Multiplier Effect: G-protein activation increases second messenger concentrations.  Role: Second messengers communicate within the cell, influencing ion channels, activating proteins, or altering chromosome activity. IONOTROPIC vs METABOTROPIC→ STRUCTURE   Ionotropic Receptors: □ Made of 5 different subunits forming a channel. □ Subunits are separate proteins.  Metabotropic Receptors: □ Single protein with 7 transmembrane domains. □ Contains intracellular and extracellular loops, with an amino and carboxyl terminal on opposite sides. CLASSES OF IONOTROPIC RECEPTORS i. Glutamate Ionotropic Receptors (3 main classes): □ AMPA receptors □ NMDA receptors □ Kainate receptors □ Different subtypes formed by varying subunit combinations. ii. GABA Ionotropic Receptor: □ GABA A receptors. iii. Acetylcholine Ionotropic Receptor: □ Nicotinic receptors (binds with nicotine in the brain). iv. Serotonin Ionotropic Receptor: □ Receptors for serotonin are ionotropic in some cases. CLASSES OF METABOTROPIC RECEPTORS  Glutamate: Metabotropic receptors present.  GABA B: Metabotropic receptor.  Dopamine: D1 and D2 metabotropic receptors.  Serotonin: 1-7 metabotropic receptors, with significant variety.  Norepinephrine & Epinephrine: Alpha (α) and Beta (β) metabotropic receptors.  Acetylcholine: □ Muscarinic metabotropic receptors. □ Nicotinic ionotropic receptor. □ Muscarinic metabotropic receptor. Note: Acetylcholine receptors are vital for the neuromuscular junction and autonomic nervous system.  GPCR- G-protein coupled receptor- METABOTROPIC RECEPTOR PEPTIDES: Substance P, Vasopressin (ADH), Orexin, Opioids (Enkephalins, Endorphins, pain relief), often co-released with other neurocrines. LIPIDS:  Endogenous Cannabinoids, CB1 receptors (brain), CB2 receptors (periphery). METABOTROPIC RECEPTORS Most common receptor type, coupled to G-proteins, no direct control of ion channels, and induce a ‘multiplier effect’ via second messengers. METABOTROPIC RECEPTORS DIFFERENT SECOND MESSENGERS, DIFFERENT EFFECTS SECOND MESSENGERS AND EFFECTS: □ Different metabotropic receptors activate different second messengers: a) cAMP b) Phosphoinositol System c) Calcium d) Arachidonic Acid System □ Each second messenger leads to distinct cellular responses. REGULATION OF GENE EXPRESSION Transcription factors: NF-kB (IkB+NF-kB > IkB+P/NF-kB), CREB (cAMP response element-binding), Cellular Immediate-Early Genes (c-fos, fosB, c-jun, junB), and third messengers. Regulation of Gene Expression: □ Transcription Factors: Proteins that turn genes on or off. NF-kB: Helps control immune responses and stress. CREB: Activated by cAMP, important for memory. Immediate-Early Genes (c-fos, fosB, c-jun, junB): Respond to stress and help with cell growth. Third Messengers: Additional molecules that help regulate gene activity. These transcription factors control how genes are activated, affecting memory, stress responses, and cell functions. SIGNAL TRANSDUCTION TO THE NUCLEUS □ Activation of metabotropic receptors by neurotransmitters triggers G-protein and second messengers. □ These signals phosphorylate proteins, which translocate to the nucleus, affecting gene expression. □ Activation of protein kinases leads to gene activation via transcription factors, influencing protein/enzyme synthesis or inhibition. □ Second messengers can also affect ion channels, pumps, and neurotransmitter receptors. □ Some genes encode third messengers that further activate downstream genes. LESSON 4- ANATOMY STRUCTURE OF THE VERTEBRATE NERVOUS SYSTEM 1. CENTRAL NERVOUS SYSTEM (CNS) □ Components: Composed of the brain and the spinal cord. 2. PERIPHERAL NERVOUS SYSTEM (PNS) □ Function: Connects the brain and spinal cord to the rest of the body.  3. SOMATIC NERVOUS SYSTEM □ Type: Voluntary Nervous System □ Function: Consists of axons that convey messages: ◊ From the sense organs to the CNS. ◊ From the CNS to the muscles. 4. AUTONOMIC NERVOUS SYSTEM □ Type: Involuntary Nervous System □ Function: Controls internal organs such as the heart, intestines, and other visceral organs. FIND YOUR WAY AROUND THE BRAIN 1. ROSTRAL - CAUDAL □ Rostral refers to the anterior (front). □ Caudal refers to the posterior (back). These terms are used to describe positions along the axis of the brain and spinal cord. 2. VENTRAL – DORSAL □ Ventral refers to the inferior (bottom) side. □ Dorsal refers to the superior (top) side. These terms are often associated with four-legged animals (quadrupeds), where: ◊ The ventral side is the belly. ◊ The dorsal side is the back. □ In humans, the brain is tilted approximately 90 degrees compared to the spinal cord due to evolutionary changes in posture (from quadrupedal to bipedal). This can make some anatomical terms seem misleading. 3. SPINAL CORD AND BRAIN COMPARISONS  When comparing the human brain to that of a four-legged animal (e.g., rat): □ Rostral (frontal) is the front of the brain. □ Caudal (posterior) is the back of the brain. □ Dorsal (superior) is the top of the brain. □ Ventral (inferior) is the bottom of the brain.  Spinal Cord Terminology: □ Ventral and dorsal terms in the spinal cord are derived from the quadrupedal anatomical orientation. □ In quadrupeds, the ventral side is the bottom (toward the belly), and the dorsal side is the top (toward the back). □ The brain's orientation changes these terms when referring to the human spinal cord. 4. TILTING OF THE SPINAL CORD AND BRAIN □ As humans evolved from four-legged animals to upright postures, the brain and spinal cord tilted about 90 degrees. This change in posture is why some anatomical terms might seem misleading. Ventral and dorsal in the spinal cord refer to the belly (ventral) and back (dorsal), respectively. 5. CORONAL, HORIZONTAL, AND SAGITTAL SECTIONS □ Coronal Section: A section that divides the brain into front (anterior) and back (posterior) parts. □ Horizontal Section: A section that divides the brain into top and bottom parts. □ Sagittal Section: A section that divides the brain into left and right parts. ANATOMICAL TERMS REFERRING TO DIRECTIONS 1. GENERAL NOTE: There is a distinction in anatomical terms when referring to the brain and spinal cord. 2. TERMS FOR DIRECTIONALITY: Term Definition Dorsal Toward the back, away from the ventral (stomach) side. The top of the brain is considered dorsal due to its position in four-legged animals. Ventral Toward the stomach, away from the dorsal (back) side. Anterior Toward the front end. Posterior Toward the rear end. Superior Above another part. Inferior Below another part. Lateral Toward the side, away from the midline. Medial Toward the midline, away from the side. Proximal Located close (approximate) to the point of origin or attachment. Distal Located further from the point of origin or attachment. Ipsilateral On the same side of the body (e.g., two parts on the left or two on the right). Contralateral On the opposite side of the body (e.g., one on the left and one on the right). 3. PLANES OF THE BRAIN: Term Definition Coronal Plane (Frontal Plane) A plane that shows brain structures as seen from the front. Sagittal Plane A plane that shows brain structures as seen from the side. Horizontal Plane (Transverse Plane) A plane that shows brain structures as seen from above. 4. STRUCTURAL TERMS IN NEUROANATOMY: Term Definition Lamina A row or layer of cell bodies separated from other cell bodies by a layer of axons and dendrites. Column A set of cells perpendicular to the surface of the cortex, with similar properties. Tract A set of axons within the CNS (central nervous system), also called a projection. If axons extend from cell bodies in structure A to synapse onto B, we say the fibers "project" from A onto B. Nerve A set of axons in the periphery, either from the CNS to a muscle or gland, or from a sensory organ to the CNS.  Nucleus A cluster of neuron cell bodies within the CNS. Ganglion A cluster of neuron cell bodies, usually outside the CNS (e.g., in the sympathetic nervous system). 5. BRAIN STRUCTURES: Term Definition Gyrus (pl. gyri) A protuberance on the surface of the brain. Sulcus (pl. sulci) A fold or groove that separates one gyrus from another. Fissure A long, deep sulcus. AFFERENT VS EFFERENT PROJECTIONS EFFERENT PROJECTIONS: □ Efferent projections are axons originating from the cell body within a structure (e.g., lateral ventricle). □ These axons send information from the structure to target tissues or other structures. AFFERENT PROJECTIONS: □ Afferent projections are axons from other structures/nuclei that project to the lateral ventricle. □ These projections bring information to the structure. CONNECTIVITY: □ A structure's connectivity is defined by: Afferent projections: Where it receives information from. Efferent projections: Where it sends information to, influencing other structures. PERIPHERY Sensory receptors in organs or skin sense internal/external stimuli and send information through the PNS to the CNS. v. CENTRAL NERVOUS SYSTEM Information is integrated, processed, and a response is coordinated. EFFECTOR RESPONSE The response is sent to effector muscles via the PNS (output division), which is divided into: □ SOMATIC DIVISION: Controls voluntary skeletal muscles. □ AUTONOMIC DIVISION: Controls involuntary organs and processes. ENTERIC NERVOUS SYSTEM (ENS) - "LITTLE BRAIN OF THE GUT" 1) Location and Function: The Enteric Nervous System (ENS) is located in the wall of the digestive tract (guts, intestines, etc.), forming a network of neurons. It regulates the function of the digestive system, including motility and secretion. 2) Regulation and Independence: Primarily regulated by the Autonomic Nervous System (ANS), which connects to the Central Nervous System (CNS). However, the ENS can also integrate stimuli from the digestive tract and coordinate responses within the gut without direct brain involvement. The brain can modulate ENS functions, such as heart rate and emotional responses, via feedback mechanisms. 3) Autonomous Function: The ENS is considered an autonomous system, capable of operating independently while still being influenced by the CNS and the Autonomic Division. FUNCTIONS OF THE NERVOUS SYSTEM 1) SENSORY INPUT: Sensory organs (eyes, ears, skin, etc.) conduct signals to information processing centers (brain and spinal cord). 2) INTEGRATION: Sensory signals are interpreted, and a response is developed in the brain and spinal cord. 3) MOTOR OUTPUT: Signals are conducted from the brain or spinal cord to effector organs (muscles or glands), which allows the body to respond to environmental stimuli. SENSORY RECEPTORS: □ Sensory input originates from sensory receptors. TRANSMISSION TO CNS: □ The sensory signals are moved to the Central Nervous System (CNS) for processing. INTEGRATION: □ In the CNS, the signals are integrated with perception, cognition, and other higher brain functions. OUTPUT: □ The processed information results in a behavioral output. INPUT TYPES: □ Outputs can be triggered by not only external stimuli but also internal stimuli, including emotional and motivational influences. THE BRAIN 1) SKULL STRUCTURE: The skull is composed of flat bones that are fused together. 2) BRAIN CORTEX: The cortex is the part of the brain located underneath the skull. 3) LOBES OF THE BRAIN: The brain is divided into distinct lobes. The name of each lobe corresponds to the bone covering it. 4) LOBES AND BONES: Frontal Lobe Parietal Lobe Temporal Lobe Occipital Lobe  THE MENINGES  The meninges are connective tissue membranes that protect the brain and spinal cord. □ There are three layers of meninges surrounding the CNS, providing protection to both the brain and spinal cord. □ The meninges consist of three distinct layers: Dura Mater: ◊ Divided into outer and inner layers. Arachnoid: ◊ Located just beneath the dura mater. Pia Mater: ◊ The innermost layer, which lines the surface of the brain and follows its grooves (sulci). PROTECTIVE FUNCTION: □ The meninges provide essential protection for the brain and spinal cord. □ They contain pain receptors, making inflammation of the meninges (meningitis) painful. RELATED CONDITIONS: □ Meningitis: Inflammation of the meninges, causing pain. □ Migraine headaches: Caused by swollen blood vessels in the meninges. SKULL AND MENINGES LAYERS i. SKULL AND DURA MATER: The skull is the bony structure that encases and protects the brain. Underneath the skull, we have the dura mater, which is the strongest outermost layer of the meninges. It consists of two layers: the outer and inner layers. 1) ARACHNOID AND PIA MATER: Arachnoid: A thinner layer beneath the dura mater, marked in purple. Pia mater: The innermost layer, shown in light blue, that closely follows the grooves and sulci of the brain. 2) MENINGEAL SPACES: Subdural space: The space between the dura mater and the arachnoid. Subarachnoid space: A larger space beneath the arachnoid, where most blood vessels run and where cerebrospinal fluid (CSF) is located. 3) CEREBROSPINAL FLUID (CSF): CSF is generated in the cavities of the brain and rises through the subarachnoid space. The arachnoid villi (valve-like structures) allow CSF to reenter the bloodstream. 4) BLOOD-BRAIN BARRIER: The vessels that penetrate the brain tissue are surrounded by a glial limiting membrane formed by glial cells, which constitute the blood-brain barrier. This barrier ensures that blood vessels do not communicate directly with brain tissue and is lined by podocytes. ii. MENINGES AND SPINAL CORD 1) Meninges in the Spinal Cord: The meninges line both the brain and the spinal cord. These protective layers continue from the brain down along the spinal cord. 2) Three Meningeal Layers: Dura mater: The outermost, strongest layer. Arachnoid: The middle, thinner layer. Pia mater: The innermost layer that follows the brain's or spinal cord's surface grooves. 3) Autonomic Nervous System Ganglia: The meninges also cover the ganglia adjacent to the spinal cord, which are part of the autonomic nervous system. 4) Inflammation: Meningitis: Inflammation of the meninges. Encephalitis: Inflammation of brain tissue, which is more severe. BRAIN SURFACE AND FOLDS 1) Convoluted Brain Structure: The human brain is convoluted, with folds (gyri) and grooves (sulci), which increase the surface area. 2) Developmental Folding: As the cerebrum grows faster than the skull during development, it causes the brain to fold back on itself, increasing surface area while keeping volume minimal. 3) Significance of Folding: More surface area means more neurons, leading to greater processing power. The brain has a walnut-like appearance, and the degree of folding correlates with processing capabilities. THE CEREBRUM AND ITS LOBES □ The cerebrum is composed of two hemispheres. □ It is the major structure of the forebrain and represents the most recently expanded feature of the mammalian CNS. NAMES OF THE LOBES AND THEIR FUNCTIONS 1) Brain Structure Overview: The cerebrum consists of two hemispheres. It originates from the forebrain and has grown to cover most subcortical structures. 2) Lobes of the Cerebrum: Frontal Lobe: ◊ Located under the frontal bone. ◊ Involved in executive functions such as decision-making, voluntary movements, and goal-directed actions. ◊ Still developing in adulthood (impulsivity in younger individuals due to incomplete development). Parietal Lobe: ◊ Located posterior to the frontal lobe. Occipital Lobe: ◊ Positioned at the back of the brain. Temporal Lobe: ◊ Found on the side of the brain. 3) Additional Information: The longitudinal fissure separates the two hemispheres. Each lobe has specialized functions. CEBRAL CIRCULATION  Blood vessels emerge from the neck, wrap around the brainstem, cerebrum, and cerebellum, and penetrate the brain.  VASCULAR SUPPLY: □ Neurons require high oxygen and glucose. Blood vessels, originating from the carotid arteries, supply both the surface and inner regions of the brain.  CAROTID ARTERIES: □ Carotid arteries branch at the brain’s base, forming smaller vessels and capillaries that enter the brain tissue.  CLINICAL RELEVANCE: □ A stroke occurs from a blockage in these vessels, disrupting blood flow to the brain. BRAIN’S INTERNAL FEATURES 1) CORONAL SLICE: A coronal slice at the cerebrum end of the spinal cord shows grey matter on the brain's surface and white matter inside. In the spinal cord, grey matter forms a butterfly shape with white matter on the sides. 2) WHITE MATTER: Composed of myelinated axons, white matter connects distant brain structures. Key bundles include the anterior commissure (ventral) and corpus callosum (dorsal), connecting the two brain hemispheres. 3) CORPUS CALLOSUM: A bundle of white matter that connects the left and right hemispheres of the brain, seen in the sagittal plane as compact white tissue. 1) VENTRICLES: The brain has ventricles filled with cerebrospinal fluid (CSF), generated by ependymal cells lining the cavities. CSF circulates through the brain and spinal cord, cushioning, providing hormones and nutrients, and removing waste. 2) FUNCTIONS OF CSF: Provides cushioning, serves as a reservoir for hormones and nutrition, and helps in waste removal from the brain and spinal cord.  3) CEREBRAL VENTRICLES: There are four ventricles: Lateral ventricles Third ventricle Fourth ventricle These ventricles contain CSF and are critical in fluid production and circulation. LATERAL VIEW OF VENTRICLES 1) LATERAL VENTRICLES: Located in the dorsal portion of the brain, there are right and left lateral ventricles. They extend from the frontal area and move backward along both sides. 2) THIRD VENTRICLE: The lateral ventricles converge in the frontal area to form the third ventricle, which moves toward the back. 3) FOURTH VENTRICLE: The third ventricle continues and becomes the fourth ventricle, which then leads to the central canal of the spinal cord. 4) CEREBRAL AQUEDUCT: The narrow passage connecting the first and fourth ventricles, allowing communication between these two systems. CEREBRAL SPINAL FLUID (CSF) FUNCTIONS AND CIRCULATION □ Functions of CSF: Source of electrolytes (sodium, potassium, calcium) crucial for maintaining resting membrane potential (RMP) and generating action potentials (AP). Protective and supportive medium. Conduit for neuro-active and metabolic products (waste removal). □ Production and Circulation: CSF is secreted by ependymal cells, primarily in the choroid plexus of the lateral and third ventricles. Circulates from the lateral ventricles to the third, then to the fourth ventricle. Moves out of the brain, into the meninges, specifically the subarachnoid space (between the arachnoid and pia mater). □ Cushioning Function: CSF provides hydrostatic protection, preventing the brain from damaging itself against the skull. It acts as a cushion, similar to water in a jar preventing tofu from breaking when shaken. □ Additional Functions: Acts as a reservoir of hormones. Provides nutrition and maintains ion concentration for neurons. EPENDYMAL CELLS □ Function: Ependymal cells secrete cerebrospinal fluid (CSF) by filtering plasma from blood vessels. □ Ion Regulation: They regulate the concentration of ions (sodium, chloride, calcium, etc.) in CSF, adjusting it compared to blood and the rest of the body. □ Location: These specialized epithelial cells are primarily found on the roofs of the ventricles. □ Barrier: Tight junctions between ependymal cells prevent CSF from spreading to adjacent tissue. □ Role: Ependymal cells ensure proper ionic balance in the brain and spinal cord by controlling CSF composition. COMPARATIVE BRAIN EVOLUTION AND DEVELOPMENT  Brain Evolution: The brain evolves across different species, with variations seen in the development stages.  Embryonic Development: In early development, a sheet forms that will become the nervous system. This sheet folds to form a neural tube.  Enlargement: The rostral (front) part of the neural tube enlarges, forming three distinct regions 1) THE PROSENCEPHALON (FOREBRAIN) 2) THE MESENCEPHALON (MIDBRAIN) 3) THE RHOMNEMCEPHALON (HINDBRAIN) 4) THE SPINAL CHORD  Spinal Cord: The rest of the tube develops into the spinal cord.  Mammalian Development: In mammals, an evolved stage shows further differentiation. The telencephalon becomes the cerebrum. MAJOR DIVISIONS OF THE VERTEBRATE BRAIN THE HUMAN BRAIN STEM: □ Cerebellum