Neurobiology Notes PDF

Neurobiology → deals with the structure and function of the nervous system - Nervous system - Central nervous system: brain + spinal cord - Peripheral nervous system: All nerves and sensory structures outside of the brain and spinal cord; connects the CNS to the rest...

Neurobiology → deals with the structure and function of the nervous system - Nervous system - Central nervous system: brain + spinal cord - Peripheral nervous system: All nerves and sensory structures outside of the brain and spinal cord; connects the CNS to the rest of the body (organs, limbs, skin) - Somatic → responsible for voluntary control of skeletal muscle - Autonomic → responsible for involuntary control of glands and smooth muscle - Sympathetic (fight or flight) & parasympathetic (rest and digest) Evolution and diversity of nervous systems Basic Nervous System: - Early nervous systems in simple organisms like cnidarians consist of a decentralized nerve net, with no central processing area (the nervous system is spread throughout the body). - More complex organisms evolved centralized systems for better coordination and processing. Centralization: → evolutionary trend where nerve cells (neurons) become concentrated in specific regions of an organism’s body, forming central processing areas, such as a brain or spinal cord. This process leads to a more organized and efficient nervous system, enabling better coordination and faster responses to stimuli. - Emergence of central nervous systems (CNS) allowed for focused processing hubs like the brain and spinal cord. - Centralization enables more efficient signal processing and faster responses. - Found in bilaterians (bilateral symmetry), with increasingly complex structures in chordates and vertebrates. Cephalization: → evolutionary trend where sensory organs and nerve cells become concentrated at the front (or head) of an organism, leading to the formation of a distinct head region. This head region typically includes a brain or a central ganglia (cluster of nerve cells) and sensory organs like eyes, ears, and olfactory (smell/taste) structures, which enable the organisms to process information about their environment more efficiently. - A specialized form of centralization involving the concentration of nervous tissue and sensory organs in the head region. - Facilitates enhanced perception, processing, and decision-making, especially in forward-moving organisms. - Prominent in higher animals, especially vertebrates, where the brain is a dominant control center. Evolutionary Trends: - Progression from diffuse nerve networks to centralized and cephalized systems corresponds with increased behavioral complexity and environmental adaptation. - Vertebrates show the most advanced cephalization, with significant development of the forebrain for cognition and sensory integration. Adaptations Across Phyla: - Insects: Centralized brain and segmental ganglia, with moderate cephalization.  - Mollusks: Diverse nervous systems; cephalopods exhibit advanced cephalization and learning abilities. - Vertebrates: High centralization and cephalization, with dominance of a large brain in most species. The Principle of Stimulus and Reaction 1. Receptors in sense organs receive stimuli (a change in the environment, e.g., light, sound, pressure, heat, chemicals) and convert them into electrical signals. 2. Sensory nerve fibers carry information as electrical signals to the central nervous system (brain + spinal cord), which understands and processes electrical signals and sends them off. 3. Motor nerve fibers conduct electrical signals from the CNS to the effector organ (e.g., muscle, gland), which leads to a reaction/response. Types of stimuli: Structure of a nervous system → Specialized cells (neurons) can produce, process, and transmit electrical impulses. They pass on information from the sensory organs to the brain and from the brain to the effector organ. 1. Sensory neurons transmit electrical impulses from receptors to the CNS—the brain and spinal cord. 2. Motor neurons transmit electrical impulses from the CNS to effectors. 3. Relay neurons transmit electrical impulses between sensory neurons and motor neurons. Structure of a (Motor) Neuron 1. Cell body a. Contains the nucleus and many organelles; main center for metabolic processes within the neuron; area of impulse input 2. Mitochondrion a. Place of cellular respiration = powerhouse of cell 3. Nucleus a. Contains DNA 4. Axon hillock a. Connects the cell body with the axon of a neuron. 5. Cell membrane a. Separates cell from outside, gas exchange 6. Dendrites a. Enlargement of cell surface area; connection to other neurons (for impulse input); pick up signals from their environment of other neurons 7. Synapse a. Connection to other cells (nerve, muscle, gland); impulse transmission to these cells 8. Axon a. responsible for transmitting impulses from the soma (cell body/cytoplasm) towards other nerve, muscle, or gland cells 9. Myelin sheath (glial cell) a. Made from Schwann cells that wrap themselves around axons and create an insulation; only found in vertebrates b. Surface area enlargement 10. Nodes of Ranvier a. Uninsulated axon areas between Schwann cells that are responsible for impulse transmission; small gaps of exposed axon (seep up transmission) 11. Axon terminal a. Thickening at the end of the axon 12. Schwann cells  a. Type of glial cell that creates the myelin sheaths How do neurons transmit electrical signals? → Through ions (K+, Na+, Cl-) Resting membrane potential - When measuring the electrical charge inside a neuron relative to the outside, the resting membrane potential is approximately -70 mV. This voltage exists only in non-stimulated axons (i.e., when no signal is being transmitted). - Ionic gradient across the membrane - Larger anions, such as negatively charged proteins synthesized within the cell, cannot diffuse through the membrane. - Ions like potassium (K⁺), sodium (Na⁺), and chloride (Cl⁻) are absorbed through food and can move in and out of the cell via specific channel proteins. - Resting membrane potential is determined by the electrochemical gradient, which comprises: - Concentration gradient: A difference in the number of particles (ions/molecules) across the membrane, which drives passive or active transport. - Electrical gradient: A difference in electrical charge across the membrane. Ions diffuse from areas of high concentration (or charge) to areas of low concentration (or charge) to balance this gradient. - Permeable Membrane - When both ions can move, concentration gradients drive equal movement (no voltage difference forms). - Semipermeable Membrane - When only one ion can move (e.g., K⁺ in KCl solution), an electrical gradient develops, and ion movement is influenced by both the concentration and electrical force. - K⁺ diffuses down its concentration gradient (a charge imbalance develops because Cl⁻ cannot follow) → The side losing K⁺ becomes negatively charged, and the side gaining K⁺ becomes positively charged → K⁺ goes against the concentration gradient as it is attracted back to the negative side. Sodium-potassium pump → The term "sodium-potassium pump" is not biochemically precise because it oversimplifies the mechanism, focusing only on ion movement. "Sodium-potassium ATPase" is more accurate, as it highlights the enzyme's ATPase activity, which drives the active transport of Na⁺ and K⁺ ions. Structure: - The pump is a transmembrane protein composed of two main subunits: 1. α-subunit: Contains the binding sites for Na⁺, K⁺, and ATP, as well as the ion transport pathway. 2. β-subunit: Stabilizes the α-subunit and helps the pump insert into the membrane. - It has ATPase activity, meaning it hydrolyzes ATP to provide the energy for active transport. Function: - Ion Binding: - On the intracellular side, 3 Na⁺ ions bind to specific sites on the pump. - ATP is hydrolyzed, transferring a phosphate group to the pump (phosphorylation). - Conformational Change: - The pump undergoes a shape change, releasing 3 Na⁺ ions outside the cell. - K⁺ Binding and Return: - 2 K⁺ ions bind from the extracellular side, and the pump dephosphorylates. - It returns to its original shape, releasing 2 K⁺ ions inside the cell. The sodium-potassium pump (Na⁺/K⁺-ATPase) plays a crucial role in maintaining and stabilizing the resting membrane potential (around -70 mV) by: - Establishing Ion Concentration Gradients: - The pump actively transports 3 Na⁺ ions out of the cell and 2 K⁺ ions into the cell per cycle. - This creates a high Na⁺ concentration outside and a high K⁺ concentration inside the cell. - These concentration gradients are essential for the resting membrane potential, as K⁺ ions primarily diffuse out of the cell (down their concentration gradient) through leak channels, leaving behind a net negative charge. - Contributing to the Negative Potential: - The pump is electrogenic because it removes 3 positive charges (Na⁺) for every 2 positive charges (K⁺) it brings in. - This unequal exchange of ions contributes a small negative charge directly to the membrane potential. - Maintaining Gradient Stability: - Without the pump, the passive leakage of Na⁺ into the cell and K⁺ out of the cell would eventually dissipate the concentration gradients, collapsing the resting potential.  - By counteracting this leakage, the pump ensures the gradients persist, enabling the neuron to maintain its resting state and be ready for action potential generation. Establishment of Resting Membrane Potential in Neurons: Ion Distribution: - The uneven distribution of ions across the membrane (high K⁺ inside, high Na⁺ and Cl⁻ outside) is crucial for establishing the resting potential. Potassium (K⁺) Leak Channels: - K⁺ leak channels, which are always open, allow K⁺ to diffuse out of the cell down its concentration gradient. - As K⁺ exits, it leaves behind negatively charged proteins and ions inside the cell, creating a net negative charge. Establishment of Electrical Gradient: - The outward movement of K⁺ generates an electrical gradient, making the interior of the cell more negative. - This results in an equilibrium potential for K⁺ (~ -102 mV), where the electrical pull balances the concentration gradient. Resting Membrane Potential (~ -70 mV): - The resting potential is slightly less negative than the K⁺ equilibrium potential due to the small contributions of Na⁺ and Cl⁻ ions, as well as the electrogenic effect of the sodium-potassium ATPase. Selective Permeability: - At rest, the membrane is mostly permeable to K⁺ through leak channels, while Na⁺ and Cl⁻ channels are mostly closed, helping maintain stability until the neuron is stimulated. Action potential  a) Channel closed during resting potential; charge = resting potential b) Channel is open; Na+ enters. c) Channel is open but inactivated (K+ channels open). d) Channel closes (opening activated), charge returns to resting potential. → All-or-none law: an action potential either happens fully or not at all, based on whether the membrane potential reaches the threshold. 1. Resting Potential: a. Membrane potential: approximately ~ -70 mV. The resting potential is maintained by… i. The sodium-potassium pump, which moves 3 Na⁺ out of the cell and 2 K⁺ into the cell using ATP ii. Always-open leak channels, which allow a small but steady flow of K⁺ out of the cell and Na⁺ into the cell, down their respective concentration gradients. b. The activation gates of the voltage-gated K+ and Na+ ion channels are closed (no K+ and Na+ flows through them), and the inactivation gates are opened on most Na+ channels. This means the channels are "ready to respond" to a stimulus if the membrane potential reaches the threshold (~ -55mV). c. State of the Neuron: The neuron is at its resting equilibrium. 2. Depolarization:  a. Membrane potential: becomes less negative as it approaches the threshold of around -55 mV. b. The activation gates on some Na+ channels open, allowing more Na+ to diffuse into the cell. This influx of positively charged ions causes more activation gates of Na+ channels to open → rapid rise in membrane potential. c. State of the Neuron: The neuron becomes more positive. 3. Rising phase & peak of action potential: a. Membrane potential: Peaks around +40 mV. b. Once the threshold is crossed, the positive-feedback cycle of Na+ influx rapidly brings the membrane potential to the action potential’s maximum. K+ channels begin to open as the peak is reached. c. State of Neuron: Inside of the neuron is more positive relative to the outside. 4. Falling phase (Repolarization): a. Membrane potential: Drops from the peak (around +40 mV) back toward a more negative value. b. Ion channels: i. The inactivation gates on most Na+ channels close, halting Na+ influx , which prevents further depolarization. ii. The activation gates on most K⁺ channels open, allowing K⁺ to rush out of the cell. c. State of the Neuron: The outflow of K+ causes the membrane potential to rapidly return to its resting state, initiating repolarization. 5. Undershoot (Hyperpolarization): a. Membrane potential: Temporarily becomes more negative than the resting potential (~ -70 mV), dipping closer to ~ -80 or -90 mV. b. Ion channels: i. Voltage-gated K⁺ channels remain open longer than needed, causing an excessive outflow of K⁺. ii. Eventually, the activation gates of K+ channels close. iii. Voltage-gated Na⁺ channels reset (activation gates close, inactivation gates reopen), preparing for the next action potential. c. State of Neuron: This hyperpolarization (undershoot) ensures that the neuron enters a refractory period, preventing immediate reactivation. As the K⁺ channels close, the membrane potential returns to the resting level (~ -70 mV). The sodium-potassium pump and leak channels restore ionic balance, fully re-establishing the resting potential. Action potential conduction → Action potentials are conducted along the axon of a neuron in one direction, from the axon hillock (or initial segment, near the cell body) toward the axon terminals. This is due to… - Refractory periods → ensures AP cannot move backward - Absolute: after an action potential passes a section of the axon, Na+ channels in the section enter their inactivated state, preventing the generation of another action potential.  - Relative refractory period → a stronger-than-normal depolarizing stimulus is needed to bring the membrane potential back to the threshold and initiate another action potential because the membrane is hyperpolarized (more negative than resting potential due to prolonged K⁺ efflux). Speed of conduction: Myelinated Axons Non-Myelinated Axons - The more myelinated the axon, the - The less myelin present, the slower faster the conduction speed. → The the signal propagates, as conduction bigger the distance between the occurs continuously rather than nodes of Ranvier, the faster the signal "jumping" between nodes. “jumps” through saltatory conduction. - The smaller the axon diameter, the - Larger axons have less internal slower the conduction speed because resistance, allowing APs to travel of higher internal resistance. faster. - Increase in temperature causes ions to diffuse faster (until 40 C) until proteins begin to denature and speed decreases. Saltatory Conduction: Continuous Conduction: Myelin Sheath Function: - There are no myelin sheaths, which is - Insulates the axon, preventing ion why the nerve impulse moves through leakage and reducing the frequency of the full length of the axon. ion exchange across the membrane. Nodes of Ranvier: - Gaps in the myelin sheath where action potentials are generated, allowing the nerve impulse to "jump" between nodes. Speed and Efficiency: - Fewer voltage-gated channels are involved, reducing delay in signal transmission. - Faster conduction enables quicker reactions and thought processes in an organism. Energy Conservation:  - Decreased ion exchange means less work for Na⁺/K⁺ pumps, saving energy needed to maintain the resting potential. Synaptic transmission → The transmission of stimuli at synapses takes place via chemical substances. 1. An action potential arrives at the axon terminal. Voltage-gated Na+ channels open, causing depolarization. 2. The depolarization causes voltage-gated Ca2+ channels in the presynaptic membrane to open.The Ca2+ concentration is greater outside the cell than inside. 3. Ca2+ enters the cell. The increase in Ca2+ inside the axon causes the vesicles containing the neurotransmitters (about 10,000 ACh molecules in one vesicle) to fuse with the presynaptic membrane and empty their contents into the synaptic cleft by exocytosis. 4. ACh molecules diffuse across the synaptic cleft and bind to receptors (ligand-gated ion channels) on the postsynaptic membrane that are normally closed. This triggers the opening of ligand-gated Na⁺ and K⁺ ion channels. → strong Na⁺ influx, weak K⁺ efflux → This depolarizes the postsynaptic membrane, producing a graded potential, which reflects the number of receptors activated. (end plate potential). 5. If the depolarization is strong enough, it spreads to regions containing voltage-gated Na⁺ channels, which, once open, trigger an action potential in the postsynaptic membrane. 6. ACh is broken down by the enzyme acetylcholinesterase (AChE) in the synaptic cleft. This closes the receptor channels, and ion flow stops, ending depolarization. 7. The products choline and acetate are taken up by the presynaptic neuron/cell to resynthesize ACh. Vesicles are recycled through endocytosis and refilled with neurotransmitter (ACh), so the neuron can prepare for the next signal. Summation = the process by which EPSPs and IPSPs are combined to influence the membrane potential. Their net effect determines whether the postsynaptic neuron fires an AP or remains inactive. The body influences whether an action potential (AP) is triggered and how strong the stimulus is perceived through several mechanisms: 1. Threshold potential and graded potentials a. Summation of graded potentials i. Spatial summation: Multiple presynaptic neurons release neurotransmitters simultaneously, combining their effects to push the postsynaptic neuron to the threshold potential. ii. Temporal summation: A single presynaptic neuron rapidly releases neurotransmitters in quick succession, allowing PSPs to add up and reach the threshold potential. b. Effect on AP triggering: Both types of summation (spatial and temporal) aim to collectively depolarize the membrane. If the combined EPSPs are strong enough to reach the threshold potential (~ -55 mV), an action potential occurs. 2. Excitatory vs. Inhibitory signals a. Excitatory postsynaptic potential (EPSP): Increase the likelihood of an AP by depolarizing the membrane (e.g., by opening Na⁺ channels). b. Inhibitory postsynaptic potential (IPSP): Decrease the likelihood of an AP by hyperpolarizing the membrane (e.g., by opening Cl⁻ channels or K⁺ channels). c. Balance of Signals: The net effect of excitatory and inhibitory signals determines whether the threshold is reached. 3. Stimulus frequency a. Stronger Stimulus → Higher Frequency of Action Potentials: i. Once the threshold is crossed, the AP always has the same magnitude (all-or-none law). However, the strength of the stimulus is encoded in the frequency of APs.  ii. A stronger stimulus generates more frequent APs, while a weaker stimulus produces fewer APs. b. Recruitment of Additional Neurons: A stronger stimulus may also activate more neurons in the area, amplifying the response. 4. Neurotransmitter release and receptor activation a. Amount of Neurotransmitter Released: A stronger stimulus leads to greater neurotransmitter release in the synapse, increasing the postsynaptic potential. b. Receptor Sensitivity: Postsynaptic cells can regulate receptor density and sensitivity, modulating their response to neurotransmitters. 5. Modulation by neuromodulators and hormones a. Neuromodulators (e.g., dopamine, serotonin) can enhance or dampen synaptic activity, altering the likelihood of AP generation. b. Hormonal Effects: Hormones like adrenaline can influence ion channel activity or receptor sensitivity, modulating excitability. 6. Neuron state (resting, refractory) a. Absolute Refractory Period: During this time, no new AP can be triggered, regardless of stimulus strength. b. Relative Refractory Period: A stronger-than-usual stimulus is required to generate an AP, as the membrane is hyperpolarized. Disruption of synaptic transmission Synapses use chemical communication and can therefore be affected by drugs, toxins, and poisons that either enhance or inhibit communication between neurons. → Neurotoxins are substances that disrupt the normal function of neurons, often leading to cell death or dysfunction. Understanding the mechanisms of neurotoxins is crucial for developing antidotes and treatments for poisoning. 1. Mimicking (Agonists): - How it works: Some substances mimic neurotransmitters and bind to the same receptors, activating them in a similar way. These substances are called agonists. - Effect: Overstimulation of the postsynaptic neuron or unintended activation of pathways. 2. Blocking (Antagonists): - How it works: Some substances bind to receptors without activating them, blocking the neurotransmitter from binding. These are called antagonists. - Effect: Inhibits or reduces the normal effect of the neurotransmitter.