Study Guide - Neuro 355 - Midterm 1 PDF

Study Guide - Neuro 355 - Midterm 1 Neurons and their Structure 1. Introduction to Neurons: o Neurons have two main parts: Soma (cell body) and Neurites (axons and dendrites). o Camillo Golgi developed a staining method in 1873 that revealed the complete str...

Study Guide - Neuro 355 - Midterm 1 Neurons and their Structure 1. Introduction to Neurons: o Neurons have two main parts: Soma (cell body) and Neurites (axons and dendrites). o Camillo Golgi developed a staining method in 1873 that revealed the complete structure of neurons. 2. Soma (Cell Body): o Contains the nucleus, cytoplasm, and organelles (e.g., mitochondria, Golgi complex). o The cytoplasm is a potassium-rich fluid that surrounds the organelles. o The nucleus contains DNA, which directs the production of proteins essential for the neuron’s function. 3. Dendrites and Axons: o Dendrites: Receive signals from other neurons (main input region). o Axon: Transmits electrical signals away from the cell body to other neurons (output region). Axons can branch to reach multiple target neurons. The Neuronal Membrane 1. Structure of the Membrane: o The membrane is made up of a phospholipid bilayer with embedded proteins. o It acts as a barrier, controlling the flow of ions in and out of the neuron, essential for generating action potentials. 2. Proteins in the Membrane: o Neurotransmitter receptors: Involved in chemical signaling. o Ion channels: Allow ions to flow across the membrane, generating electrical signals. o Ion pumps: Help maintain the neuron’s internal environment (e.g.: more potassium inside than outside). The Nucleus and Genetic Material 1. The Nucleus: o Contains genetic material (DNA).  o The nucleus is enclosed by the nuclear envelope, which has pores for the movement of materials (mRNA) in and out of the nucleus. 2. DNA and Chromosomes: o Human cells contain 46 chromosomes (23 pairs), which hold the genetic blueprint for the cell. o The DNA double helix is made up of nucleotide bases (Adenine, Guanine, Thymine, Cytosine), which pair up to form the genetic code (A-T, G-C). 3. Gene Expression: o Transcription: The process where DNA is copied into mRNA in the nucleus. RNA is similar to DNA, except that Uracil replaces Thymine). o Translation: mRNA is then read by ribosomes in the cytoplasm (e.g., rough ER) to assemble proteins, the building blocks of neurons. Cytoskeleton 1. The Cytoskeleton: o The cytoskeleton maintains the neuron’s structure and includes: ▪ Microtubules: Hollow tubes made of tubulin that run down neurites. ▪ Neurofilaments: Provide structural strength. ▪ Microfilaments: Contain actin, adjust the shape of the cell dynamically. Mitochondria and Energy Production 1. Mitochondria: o Known as the power plant of the neuron, mitochondria generate ATP (adenosine triphosphate), the energy currency of the cell. o ATP is produced from pyruvic acid and oxygen (O2). Protein Synthesis and Its Importance 1. Proteins: o Proteins determine the structure and function of neurons (e.g., ion channels, receptors). o They are made up of chains of amino acids linked by peptide bonds. 2. Protein Synthesis: o Involves two steps: ▪ Transcription (DNA to mRNA in the nucleus). ▪ Translation (mRNA to protein at the ribosome). Neuronal Architecture 1. Axons: o Neurons have only one axon, which can be very long (up to 1 meter in humans). o Axonal Structure: ▪ No rough ER, no ribosomes, and different proteins compared to the soma. ▪ Axons end in axon terminals (boutons) where synapses form. ▪ Microtubules transport materials up and down the axon. ▪ Anterograde transport: Uses kinesin to move materials down the axon. ▪ Retrograde transport: Uses dynein to bring materials back to the soma. 2. Dendrites: o Dendrites act as the "antennae" of neurons, receiving input. o Dendritic Spines: Small protrusions that increase the surface area for synapses to form 3. Synaptic Structures: o Synapse: The point of communication between neurons. o Synaptic Vesicles: Store neurotransmitters in the axon terminals for communication with other neurons. Classification of Neurons 1. Based on Number of Neurites: o Unipolar, bipolar, or multipolar based on the number of extensions from the soma. 2. Based on Dendrite Shape and Size: o Pyramidal vs. stellate neurons. o Spiny vs. aspinous dendrites (spines or no spines on dendrites). 3. Based on Connections: o Motor neurons: Carry signals to muscles. o Sensory neurons: Relay sensory information. 4. Based on Axon Length: o Golgi type I: Long axons. o Golgi type II: Short axons. 5. Based on Neurotransmitters: o Neurons can be classified by the type of neurotransmitter they release (e.g., dopamine, serotonin, norepinephrine). Glial Cells (Supporting Cells of the Nervous System)  1. Astrocytes: o Functions: ▪ Provide physical support to neurons. ▪ Regulate the extracellular environment and help form the blood- brain barrier (BBB). ▪ Can influence neurotransmission by regulating neurotransmitter concentrations. 2. Oligodendrocytes: o Found in the CNS (Central Nervous System). o Provide myelination for multiple axons, increasing the speed of action potential propagation. 3. Schwann Cells: o Found in the PNS (Peripheral Nervous System). o Provide myelination for a single segment of an axon. o Gaps between segments are called Nodes of Ranvier, essential for saltatory conduction. 4. Microglia: o Act as the immune defense system in the CNS, removing debris and protecting neurons from pathogens. The Blood-Brain Barrier (BBB) Function: o Protects the brain by tightly regulating the substances that can pass from the bloodstream into the brain. o The BBB ensures that the brain remains in a tightly controlled environment necessary for neuronal function. o Selective Permeability: Only certain substances can cross (e.g., oxygen, glucose). o Exception: Areas like the area postrema are exposed to blood and help detect toxins (trigger vomiting). Neuron Doctrine vs. Reticular Theory 1. Neuron Doctrine (Santiago Ramón y Cajal): o Neurons are discrete cells that communicate via synapses. 2. Reticular Theory (Camillo Golgi): o Neurons are part of a continuous network of cells. 3. Modern Understanding: o Cajal was mostly correct, but there are rare exceptions, such as gap junctions, where neurons can be electrically coupled and act as a continuous network. Resting Membrane Potential (RMP) 1. Introduction to Resting Membrane Potential: o Neurons transmit information over distances using electrical signals. o The resting membrane potential (RMP) is the voltage difference across the membrane when the neuron is not transmitting signals, typically around -65mV. Electrical Potentials: 1. What is Potential?: o The concept of potential refers to the capacity to generate movement or force, akin to an archer’s bow being ready to release an arrow. o In neurons, this is the difference in electrical charge across the membrane, creating a voltage. Ion Concentrations and Membrane Permeability: 1. Ion Distribution: o At rest, Na+ (sodium) and Cl- (chloride) are more concentrated outside the cell. o K+ (potassium) is more concentrated inside the cell. 2. Semi-permeable Membrane: o The neuronal membrane is selectively permeable: ▪ Lipid-soluble molecules and small uncharged molecules can cross. ▪ Ions cannot cross freely due to their interaction with water molecules, forming larger "hydration spheres" that prevent them from passing through the lipid bilayer. 3. Ion Channels: o Ions move through channels, which are selective for different ions (based on charge or size) and can open or close (gating). Forces Acting on Ions: 1. Concentrational (Diffusion) Force: o Ions move down their concentration gradient (from high to low concentration). 2. Electrostatic (Voltage) Force: o Ions are attracted to areas with an opposite charge (positive ions are attracted to negatively charged areas and vice versa).  3. Balance of Forces: o The resting membrane potential is maintained by the balance between the diffusion and electrostatic forces. Equilibrium Potential and the Nernst Equation: 1. Equilibrium Potential (Eion): o The equilibrium potential is the electrical potential at which the diffusional and electrostatic forces for a specific ion balance out, preventing further movement of that ion across the membrane. 2. Nernst Equation: o Used to calculate the equilibrium potential for individual ions. For example: ▪ EK (equilibrium potential for potassium) is approximately -80 mV. ▪ ENa (equilibrium potential for sodium) is approximately +58 mV. Resting Membrane Potential Calculation: 1. Contribution of K+ and Na+: o The RMP is closer to EK because the membrane is much more permeable to K+ than to Na+ (approximately 40 times more permeable). o The slight pull toward ENa reflects the small contribution of Na+ channels. 2. Goldman Equation: o This equation accounts for multiple ions and their permeabilities, unlike the Nernst equation which only calculates for a single ion. o The Goldman equation is essential for determining the RMP in neurons since both K+ and Na+ influence the resting potential. The Na+/K+ Pump: 1. Maintaining Gradients: o The Na+/K+ pump actively transports 3 Na+ out of the cell and 2 K+ in, maintaining the concentration gradients across the membrane. o This process uses ATP because it works against the ions' concentration gradients. Astrocytes and Potassium Regulation:  1. Role of Astrocytes: o Astrocytes help regulate the concentration of K+ in the extracellular space, preventing dangerous increases in K+ concentration which could disturb the RMP. o Excess K+ is absorbed by astrocytes and dissipated across a large area. Action Potential Overview 1. Definition: o An action potential (AP) is a rapid, transient change in membrane potential that propagates along the axon. o The AP travels down the axon to activate synaptic terminals, causing neurotransmitter release. 2. Importance: o It’s the key mechanism neurons use to communicate with one another across long distances. Threshold and Generator Potentials: 1. Threshold: o The AP is triggered when the membrane reaches a threshold level of depolarization, usually driven by generator potentials. 2. Generator Potentials: o These can be produced either chemically (via neurotransmitters) or mechanically (e.g., stretching in sensory neurons). o When enough Na+ channels are opened, the AP is triggered, making it an all-or-none event. Phases of the Action Potential: 1. Depolarization (Rising Phase): o Triggered by voltage-gated Na+ channels opening, allowing Na+ to rush in. o Membrane potential rapidly moves toward ENa (positive potential), but never fully reaches it due to Na+ channel inactivation. 2. Peak of the Action Potential: o The h-gate (inactivation gate) of Na+ channels closes, stopping further Na+ influx. o K+ channels open. 3. Repolarization (Falling Phase):  o Voltage-gated K+ channels open, allowing K+ to exit the cell, returning the membrane potential toward EK. o This repolarizes the membrane. 4. Undershoot (Hyperpolarization): o The membrane potential temporarily becomes more negative than the resting potential due to the continued opening of K+ channels. o Na+ channels deinactivate, and K+ channels are slowly closing. Refractory Periods: 1. Absolute Refractory Period: o During repolarization, the neuron cannot fire another AP because Na+ channels are inactivated. 2. Relative Refractory Period: o A stronger-than-normal stimulus is required to generate another AP since the membrane is hyperpolarized (Undershoot). Propagation of the Action Potential: 1. Saltatory Conduction: o In myelinated axons, the action potential jumps from one Node of Ranvier to the next. o This speeds up the conduction of the AP down the axon. 2. Non-myelinated Axons: o In non-myelinated axons, the AP travels more slowly, propagating along the axon in a continuous manner. The only way to speed up conduction is to augment the axon’s diameter. Voltage-Gated Channels: 1. Na+ Channels: o Made up of 4 domains, these channels open in response to depolarization and inactivate shortly after. 2. K+ Channels: o Voltage-gated K+ channels open more slowly and stay open longer, allowing K+ to exit and repolarize the cell. Clinical Relevance:  1. Local Anesthesia: o Drugs like lidocaine block Na+ channels, preventing the initiation of action potentials in sensory neurons, thus blocking pain signals from reaching the brain. Summary of Action Potential Mechanism: 1. Resting State: Na+ channels closed, voltage-gated K+ channels are also closed. 2. Rising Phase (Depolarization): Na+ channels open, Na+ enters the cell, depolarizing the membrane. 3. Falling Phase (Repolarization): Na+ channels inactivate, K+ channels open, and K+ exits the cell. 4. Undershoot (Hyperpolarization): More K+ channels open than at rest, causing the membrane potential to go below resting levels. Overview of Synaptic Transmission: 1. Action Potential Arrival: o The action potential is initiated at the axon hillock and travels down the axon, eventually reaching the axon terminal. o This triggers synaptic communication with the next neuron at the synapse. 2. Types of Synapses: o Electrical Synapses: Use gap junctions to allow direct ion flow between cells. These synapses are bi-directional and fast, but relatively rare in the central nervous system (CNS), mainly found where synchronized activity is needed (e.g., the heart). o Chemical Synapses: Utilize neurotransmitters to communicate between neurons. These synapses are more common and allow for complex signaling (amplification and diversification of the signal). Electrical Synapses (Gap Junctions): 1. Structure and Function: o Formed by connexons that create a direct channel between adjacent neurons. o Ions (and other small molecules) can pass directly from one cell to another. o These allow synchronization of neuronal activity (e.g., in oscillations or fast synchronized responses). 2. Characteristics: o Bidirectional ion flow. o Extremely fast communication.  o Common in systems that require synchronized firing, like in certain parts of the brain and heart. Chemical Synapses: Structure of the Synapse: o The synaptic cleft is about 20-50 nm wide and filled with fibrous extracellular proteins that help keep the neurons aligned. o Synaptic vesicles (50 nm in diameter) store neurotransmitters. o Larger vesicles (100 nm) known as secretory granules or dense-core vesicles contain peptides and other larger molecules. Synaptic Arrangements in the CNS: 1. Axodendritic: The synapse occurs between the axon of one neuron and the dendrite of another. 2. Axosomatic: The synapse occurs between the axon of one neuron and the soma (cell body) of another. 3. Axoaxonic: The synapse occurs between the axon of one neuron and the axon of another. Advantages of Chemical Synapses: 1. Signal Amplification: o A single action potential can trigger a large postsynaptic response, something not possible in electrical synapses. Many target neurons can be reached in the case of neuromodulators. 2. Diversity in Responses: o Different neurotransmitters and receptors allow for excitatory, inhibitory, or modulatory responses. o Responses can vary in speed, from fast to slow, adding complexity to information processing in the CNS. The Neuromuscular Junction (NMJ): 1. Characteristics: o The NMJ is a highly studied synapse between a motor neuron and a muscle fiber. o It’s extremely reliable—every action potential in the neuron leads to an action potential in the muscle. 2. Synaptic Structure: o Junctional folds in the muscle membrane contain receptors aligned with presynaptic terminals. o The neurotransmitter at the NMJ is acetylcholine (ACh), which binds to receptors on the muscle fiber to induce contraction. Neurotransmitter Release: 1. Steps of Release: o When the action potential arrives at the terminal, voltage-gated calcium (Ca2+) channels open. o Ca2+ enters the presynaptic terminal and triggers vesicle fusion with the membrane, releasing neurotransmitter into the synaptic cleft through exocytosis. Presynaptic Facilitation and Inhibition: 1. Axo-Axonic Synapses: o These synapses modulate the activity of the presynaptic terminal. o Inhibition: Reduces Ca2+ influx, decreasing neurotransmitter release. o Facilitation: Increases Ca2+ influx, enhancing neurotransmitter release. Termination of Synaptic Transmission: 1. Mechanisms: o Enzymatic degradation (e.g., acetylcholinesterase breaking down ACh). o Reuptake: Neurotransmitters are taken back into the presynaptic terminal for reuse. o Uptake by glial cells: Glial cells help clear excess neurotransmitter from the synaptic cleft. 2. Example: The enzyme acetylcholinesterase efficiently degrades ACh at the NMJ. Inhibiting this enzyme leads to continuous stimulation, causing muscle spasms. Postsynaptic Effects of Neurotransmitters 1. Neurotransmitter Binding: o After the neurotransmitter diffuses across the synaptic cleft, it binds to postsynaptic receptors. o This binding is highly specific, working like a lock-and-key mechanism, where the shape of the transmitter and the receptor must match. 2. Types of Postsynaptic Receptors: o Ionotropic Receptors (e.g., acetylcholine receptor): These are ligand- gated ion channels that open when the neurotransmitter binds, allowing ions to flow in or out of the cell. o Metabotropic Receptors (G-protein-coupled receptors): These receptors activate intracellular signaling cascades (often involving second messengers) than can open ion channels, rather than directly opening the channels. The Acetylcholine Receptor (AChR) 1. Structure: o The ACh receptor is made up of 5 subunits, including 2 alpha subunits where acetylcholine (ACh) binds. 2. Activation of AChR: o When ACh binds to the receptor’s alpha subunits, the channel opens, allowing Na+ to enter the postsynaptic cell, leading to depolarization. Excitatory and Inhibitory Post-Synaptic Potentials (EPSPs & IPSPs) 1. EPSPs (Excitatory Post-Synaptic Potentials): o Generated by the opening of channels permeable to Na+ (and sometimes K+ too), allowing Na+ to enter the cell. o These potentials depolarize the membrane and bring it closer to the threshold for firing an action potential. 2. IPSPs (Inhibitory Post-Synaptic Potentials): o Generated by the opening of channels permeable to Cl- (under certain conditions) or K+. o These potentials hyperpolarize the membrane, making it less likely for the neuron to fire an action potential. Synaptic Integration 1. Summation of EPSPs: o A single EPSP is usually too small to trigger an action potential on its own. o Temporal Summation: Multiple EPSPs can be summed over time. o Spatial Summation: EPSPs from different synapses can be combined to reach the action potential threshold. 2. Decay of EPSPs with Distance: o EPSPs are graded events, meaning they decay as they travel across the dendrites. o The length constant (λ) is the distance over which the EPSP decreases to 37% of its original value. The higher the λ, the more excitable the neuron is. 3. Excitable Dendrites: o Some dendrites are excitable, meaning they can boost EPSPs as they travel toward the soma, enhancing the chances of triggering an action potential. Metabotropic Receptors and EPSP Modulation 1. Modulation of EPSPs by Metabotropic Receptors: o For example, Norepinephrine β receptors can close K+ channels, making the membrane less leaky, increasing the length constant (λ), and enhancing the effect of EPSPs. Postsynaptic Inhibition 1. Inhibitory Postsynaptic Potentials (IPSPs): o IPSPs can counteract the effects of EPSPs, reducing the likelihood of an action potential firing. 2. Shunting Inhibition: o Inhibitory synapses located along the dendrites can "shunt" or block EPSPs before they reach the soma, effectively canceling out excitatory input.