Synaptic transmission 2: CNS synapses

lecture 5?

Chemical synapse basic requirements

All chemical synapses require neurotransmitter synthesis, vesicle packaging, calcium-dependent release, and postsynaptic receptors.

NMJ neurotransmitter

The neuromuscular junction uses only acetylcholine (ACh) as its neurotransmitter.

CNS neurotransmitters

The CNS uses many neurotransmitters (e.g., glutamate, GABA, glycine, dopamine), enabling diverse signalling.

Synaptic divergence

A single neuron sends outputs to many others, common in CNS networks.

Synaptic convergence

A single CNS neuron receives synaptic input from many different neurons.

CNS synaptic response variability

CNS neurons vary their output depending on multiple simultaneous inputs and inhibitory/excitatory balance.

EPSP definition

A small depolarisation of a postsynaptic neuron due to excitatory neurotransmitter action.

Inhibitory post synaptic potential (IPSP) definition

A hyperpolarisation or stabilisation of the membrane due to inhibitory neurotransmitter action.

Why CNS EPSPs are small

CNS synapses are small, release fewer vesicles, and contain fewer postsynaptic receptors compared with the NMJ.

EPSP propagation limits

Dendrites passively conduct signals and EPSPs decay before reaching the soma unless many summate.

Temporal summation

Multiple EPSPs arriving in rapid succession add together to reach threshold.

Spatial summation

EPSPs from different synapses combine to bring the membrane toward threshold.

Glutamate at CNS synapses

The primary excitatory neurotransmitter in the CNS, acting mainly at AMPA, NMDA, and Kainate receptors.

AMPA receptor function

A ligand-gated ion channel permeable to Na⁺ and K⁺; mediates fast excitatory synaptic currents.

NMDA receptor properties

A glutamate receptor that is both ligand- and voltage-gated; important in plasticity (though beyond scope here).

Glycine inhibitory synapses

In the spinal cord, glycine is the main inhibitory neurotransmitter, crucial in reflex circuits in animals and humans.

GABA inhibitory synapses

In the brain, GABA acting on GABA A receptors mediates most fast inhibition.

GABA A receptor function

Ligand-gated ion channel permeable to Cl⁻ that generates IPSPs; clinical target for benzodiazepines and barbiturates.

Effect of Cl⁻ conductance

Opening of Cl⁻ channels clamps membrane potential near E_Cl, preventing unwanted excitation.

How can a neurotransmitter be both excitatory & inhibitory?

Depending on the receptor subtype it binds to.

Receptor dependent

Metabotropic receptors

G-protein-coupled receptors that modulate VGICs indirectly, causing slower, modulatory EPSPs or IPSPs.

Example of mixed glutamatergic signalling

Glutamate can excite via AMPA receptors while simultaneously inhibiting via metabotropic glutamate receptors.

Knee jerk reflex central synapse

Sensory afferents release glutamate onto AMPA receptors on extensor motor neurons, generating EPSPs.

Reciprocal inhibition in reflexes

Sensory afferents also activate inhibitory interneurons that release glycine onto flexor motor neurons, reducing antagonist contraction.

Veterinary relevance – reflex testing

In horses, dogs, and cats, altered patellar reflexes may indicate spinal cord lesions at L3–L4, similar to humans but often used more diagnostically in non-verbal patients.

Veterinary relevance – glycinergic inhibition

Glycine receptor dysfunction in animals can cause exaggerated startle responses (e.g., “shaker” calves), illustrating importance of spinal Cl⁻-mediated inhibition.

CNS synaptic complexity

CNS synapses vary in neurotransmitter type, receptor variety, synaptic location, and plasticity, supporting complex behaviours and learning.