L 3 SYTBTIC TRANSMATION

Neuron Anatomy

• Neurons are the basic units of the nervous system, responsible for communication.
• They have distinct parts:
  • Cell body (soma): Contains the nucleus and other organelles.
  • Dendrites: Branching structures that receive incoming signals from other neurons.
  • Axon: A long, slender projection that propagates action potentials away from the cell body.
  • Synaptic terminals: Specialized structures at the end of the axon that release neurotransmitters, converting electrical signals into chemical ones.

Electrochemical Gradients and Membrane Potential

• The membrane potential is the difference in electrical charge across the plasma membrane of a neuron.
• This difference is maintained by ion concentration gradients and ion charge gradients.
• Resting membrane potential (RMP): The membrane potential of a neuron at rest, typically around -70mV.
  • This negativity is due to the higher concentration of potassium ions (K+) inside the cell and sodium ions (Na+) outside the cell.
  • Sodium-potassium pump (Na+/K+ ATPase): Maintains the concentration gradients by actively transporting Na+ out of the cell and K+ into the cell.
  • Leak channels: Allow for a small, passive movement of ions across the membrane, contributing to the RMP.

Changes in Membrane Potential

• Depolarization: A decrease in the negative charge inside the cell, typically caused by an influx of positive ions like sodium (Na+)
  • Depolarizations often lead to excitation.
• Hyperpolarization: An increase in the negative charge inside the cell, typically caused by an efflux of potassium ions (K+) or an influx of negative ions like chloride (Cl-).
  • Hyperpolarizations often lead to inhibition.

Excitation and Inhibition

• Excitatory postsynaptic potential (ePSP): A depolarization of the post-synaptic membrane, triggered by the binding of excitatory neurotransmitters to post-synaptic receptors.
  • Occurs when positive ions like Na+ or Ca2+ flow into the cell.
• Inhibitory postsynaptic potential (iPSP): A hyperpolarization of the post-synaptic membrane, triggered by the binding of inhibitory neurotransmitters to postsynaptic receptors.
  • When positive ions (e.g., K+) flow out of the cell or negative ions (e.g., Cl-) flow into the cell.

Summation

• Spatial summation: The combined effect of multiple synaptic inputs arriving at different locations on the postsynaptic neuron.
  • If the combined effect of all inputs is strong enough to reach the action potential threshold, an action potential will be generated.
• Temporal summation: The combined effect of multiple synaptic inputs arriving close together in time at a single location on the postsynaptic neuron.
  • If the sum of the inputs reaches the action potential threshold, an action potential will be generated.

Action Potential

• Action potential (AP): A brief, rapid, and large change in membrane potential that travels down the axon.
  • The AP is initiated when the membrane potential reaches the action potential threshold, usually around -55mV.
• Voltage-gated sodium channels (VGSCs): Open during depolarization, allowing Na+ to rush into the cell, further depolarizing the membrane.
• Voltage-gated potassium channels (VGPCs): Open near the peak of depolarization, allowing K+ to flow out of the cell, repolarizing the membrane.
• Refractory period: A brief period following an action potential during which the neuron is less likely to fire another action potential.
  • Absolute refractory period: No stimulus, regardless of its strength, can trigger another action potential.
  • Relative refractory period: Only a very strong stimulus can trigger another action potential.

Action Potential Propagation

• APs travel down the axon in a unidirectional manner, moving away from the cell body towards the axon terminal.
• The depolarization of one segment of the axon triggers the opening of VGSCs in adjacent segments, causing the AP to propagate along the axon.

Myelin

• Myelin: A fatty sheath that insulates axons, increasing the speed of action potential conduction.
  • Oligodendrocytes: Produce myelin in the central nervous system (CNS).
  • Schwann cells: Produce myelin in the peripheral nervous system (PNS).
• Nodes of Ranvier: Gaps in the myelin sheath where VGSCs are concentrated.
• Saltatory conduction: The rapid jumping of APs from one node of Ranvier to the next, speeding up conduction.
• Demyelination: Loss of myelin, often associated with diseases like multiple sclerosis, can disrupt the speed and efficiency of neural communication.

Synaptic Transmission

• Synapse: The junction between the pre-synaptic neuron and the post-synaptic neuron.
• Synaptic cleft: The narrow gap between the pre-synaptic and post-synaptic membranes where neurotransmitters are released.
• Synaptic vesicles: Small sacs within the pre-synaptic terminal that store neurotransmitters.
• Neurotransmitters: Chemical messengers that transmit signals from one neuron to another.
• Neurotransmitter receptors: Proteins on the post-synaptic membrane that bind to neurotransmitters, triggering a response in the post-synaptic neuron.

Neurotransmitter Release

• Action potential reaches the pre-synaptic terminal.
• Depolarization opens voltage-gated Ca2+ channels.
• Ca2+ influx triggers the fusion of synaptic vesicles with the pre-synaptic membrane, releasing neurotransmitters into the synaptic cleft.

Neurotransmitter Actions

• Neurotransmitters diffuse across the synaptic cleft and bind to receptors on the post-synaptic membrane.
• Ionotropic receptors: Directly open ion channels, leading to rapid changes in membrane potential.
• Metabotropic receptors: Activate G-proteins, which can modulate ion channels or trigger intracellular signaling pathways, leading to slower and more complex changes in cell function.

Neurotransmitter Inactivation

• Enzymatic degradation: Neurotransmitters are broken down by enzymes in the synaptic cleft.
• Reuptake: Neurotransmitters are transported back into the pre-synaptic neuron or taken up by neighboring glial cells.
• Diffusion: Neurotransmitters can diffuse away from the synaptic cleft.

Major Neurotransmitters

• Acetylcholine (ACh): Plays a role in learning, memory, and muscle contraction.
• Catecholamines:
  • Dopamine (DA): Involved in movement, reward, and motivation.
  • Noradrenaline (NA) / (Nor)epinephrine: Involved in alertness, arousal, and mood.
  • Adrenaline (A): Involved in stress response and energy mobilization.
• Indolamines:
  • Serotonin (5-HT): Involved in mood, sleep, and appetite.
  • Histamine: Involved in alertness, immunological responses, and gastric acid regulation.
• Glutamate (L-Glu): Major excitatory neurotransmitter.
• γ-amino-butyric acid (GABA): Major inhibitory neurotransmitter.
• Glycine (L-Gly): Inhibitory neurotransmitter.

Neurotransmitter Receptors

• Ionotropic receptors: Directly open ion channels, leading to rapid changes in membrane potential.
  • Acetylcholine (ACh): Nicotinic receptors
  • GABA: GABAA receptors
  • Glutamate: NMDA, AMPA, and Kainate receptors.
• Metabotropic receptors: Activate G-proteins leading to slower and more complex changes in cell function.
  • Acetylcholine (ACh): Muscarinic receptors
  • Dopamine (DA): D1-like (D1, D5) and D2-like (D2, D3, D4) receptors
  • GABA: GABAB receptors
  • Glutamate: mGluR1-8 receptors
  • (Nor)adrenaline (NA) / (Nor)epinephrine: α1, α2, β1, β2 receptors
  • Serotonin (5-HT): 5-HT1, 2, 4-7 receptors
  • Others: Histamine, glycine, aspartate receptors

Co-transmission: Neuropeptides

• Neuropeptides: Peptide neurotransmitters often released together with small-molecule neurotransmitters.
  • Stored in dense-core vesicles.
  • Examples: Substance P (pain perception), endorphins, enkephalins, dynorphins (opioid peptides), neurotensin, neuropeptide Y, vasoactive intestinal polypeptide (VIP).
• Neurotransmission vs. Neuromodulation:
  • Neurotransmission: Rapid communication via small-molecule neurotransmitters.
  • Neuromodulation: Slow, longer-lasting effects mediated by neuropeptides, modifying the activity of neural circuits.
• Co-transmission: The combined action of small-molecule neurotransmitters and neuropeptides allows for flexible and nuanced responses to stimuli.

Learning Outcomes

• Understand the structure and function of the synapse and its role in neuronal communication.
• Identify common neurotransmitters and their receptors in the CNS.
• Explain the mechanisms of excitatory and inhibitory postsynaptic potentials.
• Describe the components of an action potential and how it is generated and propagated.
• Understand the concept of summation and how it contributes to action potential generation.
• Explain the steps involved in synaptic neurotransmission and the role of co-transmission.

Neuron Structure and Function

• Dendrites: Receive incoming signals from other neurons.
• Resting Membrane Potential (RMP): The electrical charge difference across the neuron's membrane when it's at rest, typically around -70 mV.
• Depolarization: The process of the neuron's membrane potential becoming less negative due to an influx of positively charged ions, primarily sodium (Na⁺).
• Excitatory Postsynaptic Potential (ePSP): A depolarization of the postsynaptic membrane, making it more likely to fire an action potential, caused by an influx of positively charged ions.
• Refractory Period: A period following an action potential where the neuron is less likely to fire another action potential. This prevents the action potential from traveling backwards.
• Action Potential Propagation:
  • Threshold: The minimum level of depolarization needed for an action potential to occur.
  • Voltage-gated Sodium (Na⁺) Channels: Open first when the threshold is reached, causing a rapid influx of Na⁺ ions.
  • Myelination: The insulation of axons by a fatty sheath, allowing for faster transmission of action potentials via "saltatory conduction" (jumping from one node of Ranvier to the next).

Neurotransmitters

• Substance P: A neurotransmitter peptide involved in pain perception.
• Potassium (K⁺): The ion primarily responsible for establishing the resting membrane potential.
• Serotonin: A neurotransmitter involved in mood regulation and often targeted in antidepressant therapies.

Neuron Function and Action Potentials

• Na+/K+ ATPase Pump: This pump is critical for restoring the neuron's resting membrane potential after an action potential. It pumps out three sodium ions (Na+) for every two potassium ions (K+) that it brings into the cell, maintaining the negative charge inside the neuron.

• Absolute Refractory Period: During this period, the neuron is completely unable to fire another action potential, regardless of the stimulus strength. This ensures that action potentials travel in one direction along the axon.

• Ligand-gated Ion Channels: Neurotransmitters bind to these channels during synaptic transmission, triggering their opening. This allows specific ions to flow across the membrane, leading to either depolarization or hyperpolarization of the postsynaptic cell.

• Action Potential Propagation: After depolarization, voltage-gated Na+ channels close, and voltage-gated K+ channels open. This allows K+ to flow out of the cell, repolarizing the membrane and initiating the refractory period.

• Nodes of Ranvier: These gaps in the myelin sheath along the axon are crucial for saltatory conduction. This type of conduction allows action potentials to jump from one node to the next, significantly increasing their speed of propagation.

Synaptic Transmission

• Calcium Ions (Ca²+) Play a vital role in neurotransmitter release. When an action potential reaches the synaptic terminal, Ca²⁺ ions enter the terminal through voltage-gated Ca²⁺ channels. This influx of Ca²⁺ triggers the fusion of synaptic vesicles with the presynaptic membrane, releasing neurotransmitters into the synaptic cleft.

• Hyperpolarization: This state makes it less likely for a neuron to fire an action potential by increasing the membrane potential further away from the threshold.

• Neurotransmitters: Glycine is a primary inhibitory neurotransmitter that typically targets GABA receptors.

Synaptic Integration

• Summation: The combined effect of multiple postsynaptic potentials (PSPs) can determine whether a neuron will fire an action potential.

• Excitatory Postsynaptic Potentials (EPSPs): Depolarize the postsynaptic neuron, increasing the likelihood of an action potential.

• Inhibitory Postsynaptic Potentials (IPSPs): Hyperpolarize the postsynaptic neuron, decreasing the likelihood of an action potential.

Action Potential Threshold

• Threshold: If a neuron is stimulated to -50 mV, an action potential will not be generated because the threshold for firing has not been reached. A strong enough stimulus is needed to overcome the threshold and trigger an action potential.

Action Potentials

• During depolarization, sodium ions (Na⁺) move into the neuron, creating an inward current.
• During repolarization, potassium ions (K⁺) move out of the neuron, creating an outward current.
• The equilibrium potential (Nernst potential) for potassium (K⁺) in a neuron is typically -90 mV.
• Calcium ions (Ca²⁺) trigger the release of neurotransmitters at the presynaptic terminal through exocytosis.

Membrane Potential

• Opening ligand-gated Na⁺ channels causes the membrane potential to become less negative (depolarize).
• The driving force for Na⁺ entry when voltage-gated Na⁺ channels open is both the concentration gradient and electrical gradient.
• Influx of Cl⁻ ions when GABA binds to its receptor causes the membrane potential to hyperpolarize.
• A current of -2 mA applied to a neuron at rest (-70 mV) will cause the membrane potential to hyperpolarize.

Sodium-Potassium Pump

• The Na⁺/K⁺ pump maintains the resting membrane potential by pumping K⁺ into the cell and Na⁺ out, maintaining their concentration gradients.

Ion Effects

• Influx of K⁺ ions into a neuron due to a drug causes the neuron to hyperpolarize.

Action Potentials and Sodium Channels

• Blocking voltage-gated sodium channels prevents action potentials from occurring
• Sodium channels are responsible for the rapid depolarization phase of an action potential

Resting Membrane Potential

• Potassium (K⁺) has the highest concentration inside a typical resting neuron
• The resting membrane potential is typically around -70 mV

Neurotransmitter Effects on Membrane Potential

• Opening ligand-gated potassium channels results in hyperpolarization of the membrane

Action Potential Phases

• Repolarization is characterized by sodium channel inactivation and potassium channel opening
• Repolarization brings the membrane potential back towards the resting potential

Threshold Potential and Action Potentials

• Reaching the threshold potential triggers the opening of sodium channels, leading to an action potential

Sodium Equilibrium Potential

• The equilibrium potential for sodium (Na⁺) in a neuron is typically around +60 mV

Extracellular Potassium Concentration and Neuronal Excitability

• Increased extracellular potassium concentration decreases the resting membrane potential, making neurons less excitable

Repolarization Current

• Outward potassium current is responsible for the repolarization phase of an action potential

Neurotransmitter Role in Synaptic Transmission

• Neurotransmitters bind to receptors on the postsynaptic neuron, initiating ionic currents
• These ionic currents can either excite or inhibit the postsynaptic neuron

Chloride Ion Influx and Synaptic Signalling

• An influx of chloride (Cl⁻) ions in a postsynaptic neuron leads to hyperpolarization, thus inhibiting neuronal firing

Explore the intricate anatomy of neurons, the fundamental units of the nervous system. Understand the structure and function of key components like the cell body, dendrites, and axon, along with the essential concepts of electrochemical gradients and resting membrane potential.