Neural Physiology: Chemical Synapses, Neurotransmitters, and Post-Synaptic Responses

Neural Physiology: Chemical Synapses & Neurotransmitters

Introduction to Synaptic Transmission

Neural communication involves the transfer of information both within a single neuron and between neurons. While electrical signals (action potentials) travel within a neuron, information is transmitted between neurons at specialized junctions called synapses. Most synapses in the nervous system are chemical synapses, where electrical signals are converted into chemical signals via neurotransmitter release.

Structure of a Synapse

• Presynaptic axon terminal: The end of the neuron sending the signal, containing synaptic vesicles filled with neurotransmitter (NT).

• Synaptic cleft: The small gap between the presynaptic and postsynaptic cells.

• Postsynaptic neuron: The cell receiving the signal, equipped with receptors for neurotransmitters.

• Voltage-gated Ca2+ channels: Located in the presynaptic terminal, these open in response to an action potential.

Types of Synapses by Location

• Axodendritic synapse: Presynaptic axon terminal synapses onto a dendrite; impacts action potential (AP) generation.

• Axosomatic synapse: Presynaptic axon terminal synapses onto the soma (cell body); impacts AP generation.

• Axoaxonic synapse: Presynaptic axon terminal synapses onto another axon terminal; affects neurotransmitter release.

Steps in Chemical Synaptic Transmission

1. Action potential (AP) depolarizes the axon terminal.

2. Voltage-gated Ca2+ channels open.

3. Ca2+ influx triggers exocytosis of neurotransmitter (NT) from synaptic vesicles.

4. NT diffuses across the synaptic cleft.

5. NT binds to receptors on the postsynaptic cell membrane.

Post-Synaptic Responses: Receptor Types

• Ligand-gated ion channels (receptor-channels): Fast, short-acting. NT binding opens ion channels, causing rapid changes in membrane potential (depolarization or hyperpolarization).

• G protein-coupled receptors (GPCR): Slow, longer-term effects. NT binding activates second messenger pathways, which can open or close ion channels indirectly.

Synapse Location and Functional Impact

• Axodendritic & axosomatic synapses: Affect the likelihood of generating action potentials in the postsynaptic neuron.

• Axoaxonic synapses: Modulate the amount of neurotransmitter released from the presynaptic neuron.

Stimulus Strength and Action Potential Frequency

• AP frequency: The number of action potentials per second (measured in Hertz, Hz).

• Strong stimulus: Higher AP frequency → more Ca2+ influx → more NT released → larger postsynaptic potential.

• Weak stimulus: Lower AP frequency → less Ca2+ influx → less NT released → smaller postsynaptic potential.

• Key point: The frequency of APs encodes stimulus strength; amplitude does not change.

Termination of Neurotransmitter Signaling

Neurotransmitter activity must be rapidly terminated to ensure precise neural communication. There are four main mechanisms:

• Reuptake into presynaptic cells: NT is taken back up for reuse (recycling).

• Reuptake into glial cells: NT is removed from the synaptic cleft by surrounding glia.

• Enzymatic breakdown: NT is degraded by specific enzymes in the synaptic cleft.

• Diffusion: NT diffuses away from the synaptic cleft.

Major Classes of Neurotransmitters

• Acetylcholine (ACh): Synthesized from choline and acetyl-CoA; acts at cholinergic synapses.

• Amines: Derived from single amino acids (e.g., serotonin, dopamine, epinephrine, norepinephrine).

• Amino acids: e.g., glutamate (excitatory), GABA (inhibitory).

• Peptides: e.g., substance P.

• Purines: e.g., ATP.

• Gases: e.g., nitric oxide (NO).

• Lipids: Various signaling roles.

The Case of Acetylcholine (ACh)

Cholinergic Receptors

• Nicotinic receptors: Ligand-gated ion channels (receptor-channels); mediate fast, excitatory responses.

• Muscarinic receptors: G protein-coupled receptors (GPCRs); mediate slower, modulatory responses.

Termination of ACh Signaling

• Acetylcholinesterase (AChE): Enzyme in the synaptic cleft that breaks down ACh into choline and acetate.

• Choline: Transported back into the presynaptic cell for reuse.

• Acetate: Diffuses away from the synaptic cleft.

Modulation of ACh Signaling by Drugs & Toxins

• Nicotine: Agonist of nicotinic receptors; increases ACh signaling.

• Galantamine: Inhibits AChE; prolongs ACh presence in the synaptic cleft, increasing signaling.

• Curare: Nicotinic receptor antagonist; decreases ACh signaling.

• Atropine: Muscarinic receptor antagonist; decreases ACh signaling.

Post-Synaptic Responses & Pathways

Convergence and Divergence in Neural Pathways

• Divergence: One presynaptic neuron branches to affect multiple postsynaptic neurons (e.g., withdrawal reflex).

• Convergence: Many presynaptic neurons synapse onto a single postsynaptic neuron (e.g., retinal processing).

Excitatory and Inhibitory Post-Synaptic Potentials

• Excitatory Post-Synaptic Potential (EPSP): Depolarizes the postsynaptic membrane, bringing it closer to threshold for AP generation.

• Inhibitory Post-Synaptic Potential (IPSP): Hyperpolarizes the postsynaptic membrane, moving it further from threshold.

Ion Channel Effects

Channel Event	Ion Movement	Membrane Effect	EPSP or IPSP?
Opening Na+ channels	Na+ in	Depolarization	EPSP
Closing K+ channels	Less K+ out	Depolarization	EPSP
Opening K+ channels	K+ out	Hyperpolarization	IPSP
Opening Cl- channels	Cl- in	Hyperpolarization	IPSP
Closing Na+ channels	Less Na+ in	Hyperpolarization	IPSP

Integration & Modification of Signals

Summation of Post-Synaptic Potentials

• Temporal summation: Addition of two or more graded potentials from a single presynaptic neuron occurring in rapid succession.

• Spatial summation: Addition of graded potentials from multiple presynaptic neurons at the same time.

• Integration: The combined effect of EPSPs and IPSPs determines whether the postsynaptic neuron reaches threshold to fire an action potential.

Presynaptic Inhibition

• Global presynaptic inhibition: All axon collaterals of a neuron are inhibited, preventing neurotransmitter release from all terminals.

• Selective presynaptic inhibition: Only specific axon collaterals are inhibited, allowing selective modulation of neurotransmitter release.

Key Equations

• AP Frequency (Hz): $\text{AP Frequency} = \frac{\text{Number of APs}}{\text{Time (s)}}$

Summary Table: Synaptic Events and Effects

Step	Description
1	AP depolarizes axon terminal
2	Voltage-gated Ca2+ channels open
3	Ca2+ influx triggers NT exocytosis
4	NT diffuses across synaptic cleft
5	NT binds to postsynaptic receptors

Example: In the withdrawal reflex, a single sensory neuron diverges to activate multiple motor neurons, illustrating divergence. In the retina, many photoreceptors converge onto a single ganglion cell, illustrating convergence.

Additional info: These notes integrate and expand upon the provided lecture slides and text, ensuring a comprehensive, exam-focused summary of neural synaptic physiology for Anatomy & Physiology students.