Neural Communication: Synapses, Receptors, and Action Potentials — Comprehensive Study Notes

EPSPs and IPSPs

• Excitatory postsynaptic potential (EPSP): a small local depolarizing potential in the postsynaptic membrane that pushes the cell closer to the action potential threshold, increasing the likelihood that the neuron will fire an action potential.
  • In EPSPs, neurotransmitter-gated Na extsuperscript{+} channels open, letting positive Na extsuperscript{+} ions into the cell.
• Inhibitory postsynaptic potential (IPSP): a hyperpolarizing potential in the postsynaptic membrane that pushes the cell further away from the threshold, decreasing the likelihood of the neuron firing an action potential.
  • In IPSPs, neurotransmitter-gated Cl extsuperscript{−} channels open, and chloride ions (Cl extsuperscript{−}) rush into the cell, making the inside more negative.
• Resting membrane potential: typically around $V_{rest} \,\approx\,-65\ \mathrm{mV}$; EPSPs move the potential toward threshold (less negative), IPSPs move it away (more negative).
• Typical schematic values shown on slides: depolarization to about +40 mV for an EPSP during peak, and hyperpolarization toward 0 or more negative values for IPSP; these values illustrate direction rather than fixed amplitudes.
• Spatial and temporal integration of synaptic inputs determine whether an AP is reached:
  • Presynaptic neuron sends the signal via EPSP or IPSP to the postsynaptic neuron.
  • If the cumulative depolarization at the axon hillock reaches threshold, an action potential is produced.

Spatial and Temporal Summation

• Neurons integrate many inputs in two ways:
  • Spatial summation: the summing of all potentials that reach the axon hillock from locations across the cell body (dendrites and soma).
  • If the overall depolarization (sum of EPSPs and IPSPs) reaches threshold, an action potential is produced.
  • Notation: the combined effect can be written as a net membrane potential change at the hillock.
  • Temporal summation: the summing of potentials that reach the axon hillock based on time of arrival.
  • The closer in time the inputs arrive, the greater their impact and the likelihood of producing an action potential.
• Conceptual formula for summation at the axon hillock: $V<em>{ ext{hillock}}(t) = V</em>{ ext{rest}} + \sum<em>i \Delta V</em>i^{\text{EPSP}}(t<em>i) - \sum</em>j \Delta V<em>j^{\text{IPSP}}(t</em>j)$
  • An action potential is produced when $V<em>{ ext{hillock}}(t) \ge V</em>{th}$, where $V_{th}$ is the threshold.

Steps in Neurotransmission at a Chemical Synapse

1. Action potential arrives at the presynaptic axon terminal.
2. Voltage-gated calcium ($\mathrm{Ca^{2+}}$) channels in the terminal membrane open, and Ca extsuperscript{2+} ions enter.
3. Ca extsuperscript{2+} ions cause synaptic vesicles filled with neurotransmitter to fuse with the presynaptic membrane, releasing transmitter into the synaptic cleft.
4. Neurotransmitters bind to postsynaptic receptor molecules, causing ion channels to open and leading to an EPSP or IPSP.
   • Receptors may be chemically gated and may include autoreceptors on the presynaptic side that can decrease transmitter release.
5. EPSPs or IPSPs spread toward the postsynaptic axon hillock; if threshold is reached, an action potential will occur.
6. Synaptic transmission is rapidly stopped — action is brief and reflects presynaptic activity.
7. Termination mechanisms:
   • Degradation: rapid breakdown and inactivation of transmitter by enzymes (e.g., acetylcholinesterase, AChE).
   • Reuptake: transmitter is cleared from the synapse by being absorbed back into the presynaptic axon terminal via transporters; presynaptic receptors can regulate release.

Ligand-Gated Receptors and Neurotransmitter Recognition

• Ligands are molecules that fit into receptors in the extracellular space and activate or block them.
• A synapse using acetylcholine (ACh) has ligand-binding sites for ACh on postsynaptic receptor molecules in the postsynaptic membrane.
• The postsynaptic receptors determine the action of the transmitter:
  • ACh can be excitatory (opening Na extsuperscript{+} and K extsuperscript{+} channels) or inhibitory (opening Cl extsuperscript{−} channels).
• The receptor has a ligand-binding site that recognizes the transmitter.

Receptor Molecules Recognize Molecules Similar to Neurotransmitters

• Some chemicals can fit receptors in place of a neurotransmitter:
  • Antagonists: Curare and bungarotoxin block ACh receptors.
  • Agonists: Nicotine can mimic ACh on receptors, acting like the transmitter.
• ACh acts on at least four subtypes of cholinergic receptors.

Synaptic Transmission Can End Rapidly

• Transmitter action is brief and halted by:
  • Degradation: rapid breakdown and inactivation by enzymes (e.g., AChE).
  • Reuptake: transmitter is cleared by transporters back into the presynaptic terminal.
• Transporters are special receptors that bring the transmitter back inside.

Ionic Mechanisms Underlie the Action Potential

• For closely spaced depolarizing stimuli, only the first can trigger an AP; the membrane enters a refractory period.
  • Absolute refractory period: no action potentials can be produced.
  • Relative refractory period: only very strong stimulation can produce an AP.

Action Potential in Unmyelinated Axon

• Action potentials are actively propagated (regenerated) along the axon.
  • Each adjacent section is depolarized, triggering a new AP.
  • Propagation is unidirectional due to the refractory state after depolarization.
• Conduction velocity varies with axon diameter and myelination.
  • Continuous conduction along an unmyelinated axon.
  • Unmyelinated axon conduction velocity: approximately $0.5\ \text{m/s} \le v \le 10\ \text{m/s}$.

Action Potential in Myelinated Axon

• Myelin is a sheath of insulation around the axon formed by glial cells, speeding conduction.
• Node of Ranvier is a small gap in the myelin sheath.
• Saltatory conduction: the action potential travels inside the axon by jumping from node to node, greatly increasing speed.
• Myelinated axon conduction velocity: up to $v \approx 150\ \text{m/s}$.
• This rapid conduction is accompanied by the ability to propagate quickly while maintaining energy efficiency.

Connections and Implications

• These mechanisms underpin all neural signaling and are foundational for understanding neural circuits, reflexes, and higher cognitive processes.
• Pharmacological agents targeting cholinergic receptors, acetylcholinesterase, or transporter reuptake sites can profoundly affect synaptic strength and nervous system function.
• Dysfunctions in EPSP/IPSP balance, receptor function, or myelination can contribute to neurological and psychiatric conditions, illustrating the practical relevance of these concepts.

Quick Reference: Key Symbols and Values

• Resting potential: $V_{rest} \approx -65\ \mathrm{mV}$
• Threshold: $V_{th}$
• Membrane potential during summation:
  $V<em>{hillock}(t) = V</em>{rest} + \sum<em>i \Delta V</em>i^{\text{EPSP}}(t<em>i) - \sum</em>j \Delta V<em>j^{\text{IPSP}}(t</em>j)$
• Unmyelinated conduction velocity: $v \in [0.5,\ 10]\ \mathrm{m/s}$
• Myelinated conduction velocity: up to $v \approx 150\ \mathrm{m/s}$