In one breath
Synaptic transmission follows a set of rules: it runs one way only, it costs about 0.5 ms at every synapse, and it spreads out and gathers in through divergence and convergence. Inhibition is either direct (an IPSP on the postsynaptic neuron) or presynaptic (an ending on the terminal cuts its transmitter release), and either feedback, like the Renshaw cell, or feedforward. Facilitation strengthens transmission: potentials summate in time and in space, overlapping inputs occlude, and repeated use can habituate, sensitize or potentiate a synapse. Lasting changes of this kind are synaptic plasticity, the basis of learning and memory.
Builds on: Synapses and synaptic transmission · Leads to: Properties of spinal reflexes · Segmental organization of the motor system
| Property | In a line |
|---|---|
| Forward conduction | one way only, pre → post |
| Synaptic delay | about 0.5 ms per synapse |
| Divergence, convergence | one to many; many to one |
| Postsynaptic potentials | EPSP or IPSP |
| Inhibition | direct or presynaptic; feedback or feedforward |
| Facilitation and its kin | summation, occlusion; habituation, sensitization, potentiation |
| Plasticity | lasting change with use |
- Worth knowing, though not in your pages: other textbooks add three more properties. Fatigue: a synapse driven fast for long responds less and less as its store of transmitter runs down. pH: alkalosis raises neuronal excitability and acidosis lowers it. Hypoxia: even a brief loss of oxygen can stop transmission.
Law of forward conduction
- An impulse crosses a chemical synapse in one direction only, from the presynaptic to the postsynaptic neuron. This is the law of forward conduction.
- Electrical synapses break the rule: they conduct both ways.
- Worth knowing, though not in your pages: the reason is the synapse’s build. Only the presynaptic side holds transmitter vesicles, and only the postsynaptic side holds the receptors.
Synaptic delay
- Synaptic delay is the time an impulse takes to get across a synapse: about 0.5 ms.
- The time is used up by three steps: Ca²⁺ entering the knob, transmitter being released into the cleft, and the transmitter acting on the postsynaptic membrane to make a potential.
- Because each synapse adds its own delay, the total delay in a pathway tells you how many synapses it has: a monosynaptic, disynaptic or polysynaptic reflex arc.
- Worth knowing, though not in your pages: the stretch reflex is the classic monosynaptic arc; see Stretch reflex.
Divergence and convergence
- Divergence (one to many): one presynaptic neuron passes its message to many postsynaptic neurons.
- Convergence (many to one): many presynaptic neurons end on a single postsynaptic neuron.
- Both are very common in the CNS, and they are what make summation and facilitation possible.
Draw it: convergence and divergence
Draw two panels. In convergence, three presynaptic neurons send their axons to end on one postsynaptic neuron. In divergence, one presynaptic neuron’s axon branches to end on three postsynaptic neurons. Put arrows on every axon to show which way the impulse runs.
Postsynaptic potentials
- A shift of the postsynaptic membrane toward depolarization is an EPSP; a shift toward hyperpolarization is an IPSP. Their sizes and ionic basis are on Synapses and synaptic transmission.
Synaptic inhibition
- CNS neurons are wired so densely to one another that, left unchecked, even a trivial stimulus could spread to vast numbers of them. Synaptic inhibition stops this runaway spread: it keeps neurons stable and confines impulses to where they are needed.
- It is classified in two separate ways:
| Classified by | The two kinds |
|---|---|
| Site of action | direct (postsynaptic) or indirect (presynaptic) |
| Wiring of the circuit | feedback or feedforward |
Direct (postsynaptic) inhibition
- An inhibitory neuron releases its transmitter onto the postsynaptic neuron and makes an IPSP there, so the postsynaptic neuron itself is held down.
- Two examples, both acting on the anterior horn cells of the spinal cord:
- inhibition by descending inhibitory fibres in the cord;
- inhibition by afferents from the Golgi tendon organs, working through an inhibitory interneuron (see Inverse stretch reflex and muscle tone).
- In both, the presynaptic neuron releases an inhibitory transmitter.
- Worth knowing, though not in your pages: reciprocal inhibition is another standard example. The afferents that excite a muscle’s motor neurons also, through an inhibitory interneuron, inhibit the motor neurons of the opposing muscle.
Indirect (presynaptic) inhibition
- Here an inhibitory neuron ends on the presynaptic terminal itself, an axoaxonic contact. An impulse it fires a moment earlier stops the next impulse from getting across the synapse.
- The presynaptic neuron is not inhibitory. The ending on its terminal makes it release less transmitter, which is why this is called presynaptic inhibition.
- Indirect inhibition can also come from the postsynaptic neuron’s own recent firing. Having just fired, it may still be refractory, or less excitable during its after-hyperpolarization. In spinal neurons that after-hyperpolarization can last long, especially after repeated firing.
Three proposed mechanisms of presynaptic inhibition
- Cl⁻ conductance rises in the excitatory ending, so the action potential arriving there is smaller. Less Ca²⁺ enters, and less transmitter comes out.
- Voltage-gated K⁺ channels open. The outflow of K⁺ cuts the inflow of Ca²⁺.
- Release is blocked directly, whatever the Ca²⁺ entry.
GABA was the first transmitter shown to cause presynaptic inhibition, and it works through two of its three receptors:
| Receptor | How it cuts release |
|---|---|
| GABA-A | ↑ Cl⁻ conductance |
| GABA-B | via a G protein, ↑ K⁺ conductance |
- Other transmitters also inhibit presynaptically, through G-protein effects on Ca²⁺ and K⁺ channels.
Applied: baclofen for spasticity
Baclofen is a GABA-B agonist that works by presynaptic inhibition. It relieves the spasticity of spinal cord injury and multiple sclerosis, and it can be given intrathecally through an implanted pump.
| Direct | Presynaptic | |
|---|---|---|
| Acts on | postsynaptic neuron | presynaptic terminal |
| Contact | on soma or dendrite | axoaxonic |
| How | IPSP (hyperpolarization) | less transmitter released |
| Example | Golgi tendon organ via interneuron | GABA on the terminal |
- Worth knowing, though not in your pages: in presynaptic inhibition the postsynaptic neuron’s own membrane potential is left untouched. Only the one input is silenced, so this kind of inhibition is highly selective.
Draw it: direct and presynaptic inhibition
Direct: an inhibitory axon ending straight on the cell body of a postsynaptic neuron, marked with a minus sign. Presynaptic: an excitatory axon ending on a postsynaptic neuron, with a second, inhibitory axon ending on that excitatory terminal (the axoaxonic contact), marked with a minus sign. Label which neuron releases less transmitter.
Feedback inhibition: the Renshaw cell
- Renshaw cell inhibition in the spinal cord is the standard example, and it is negative feedback.
- A collateral from the motor neuron’s axon ends on a small inhibitory interneuron, the Renshaw cell. The Renshaw cell then inhibits the firing of the same motor neuron that excited it.
- A branch of the Renshaw cell also inhibits neighbouring motor neurons. This is lateral inhibition.
- Worth knowing, though not in your pages: the collateral excites the Renshaw cell with acetylcholine (through nicotinic receptors), and the Renshaw cell inhibits with glycine. Strychnine and tetanus toxin put this brake out of action, which adds to the muscle spasms both cause.
Draw it: Renshaw cell inhibition
Draw a motor neuron in the anterior horn, with its axon leaving the cord for a muscle. Before the axon leaves, branch off a recurrent collateral that curves back to a small Renshaw cell. From the Renshaw cell draw one axon back onto the same motor neuron (minus sign: feedback inhibition) and one onto a neighbouring motor neuron (minus sign: lateral inhibition).
Renshaw inhibition: which label?
By circuit, Renshaw inhibition is negative feedback (recurrent) inhibition, the label your book gives it; pick that whenever it is offered. By site, the Renshaw cell makes IPSPs on the motor neuron, so it is also a form of direct (postsynaptic) inhibition. It is never positive feedback, feedforward or presynaptic inhibition.
Feedforward inhibition
- Your book’s example is in the cerebellum. Mossy fibres excite granule cells, and the granule cells’ parallel fibres activate Purkinje cells.
- Purkinje output is inhibitory, because Purkinje cells release GABA. So exciting the mossy fibre–parallel fibre pathway ends by switching on an inhibitory output, and your book calls this feedforward inhibition.
Feedforward inhibition: the standard picture
Your book says the parallel fibres inhibit the Purkinje output, yet in its own chain they excite the Purkinje cells. In the standard account, parallel fibres excite the Purkinje cell and, at the same moment, basket and stellate cells. These inhibitory interneurons then inhibit that same Purkinje cell, so the input brings its own inhibition along, which limits how long the excitation lasts. In the exam, write the book’s chain and add the basket-cell step. The circuit itself is on Cerebellar divisions, histology and connections.
Synaptic facilitation
- Facilitation is an increase in transmission across a synapse. It usually comes from the terminal releasing more transmitter, so it is also called presynaptic facilitation.
- Mechanism: the action potential in the terminal is prolonged. Voltage-gated Ca²⁺ channels stay open longer, more Ca²⁺ enters, and more transmitter is released.
- Serotonin facilitates in this way. Released at an axoaxonic ending, it raises cAMP inside the terminal, and the resulting phosphorylation closes a group of K⁺ channels. Repolarization slows, and the action potential lasts longer.
Summation
- Synaptic potentials are graded, so they can add up. This happens in networks where many neurons share synapses.
| Temporal | Spatial | |
|---|---|---|
| Input | one knob, fired repeatedly | many knobs, fired together |
| Timing | next potential arrives before the last has faded | inputs arrive at the same time |
| Result | potentials pile up in time | converging potentials add |
- In spatial summation, if the inputs have the same sign (all excitatory, or all inhibitory), their combined response is larger than any one of them gives alone.
- Either way, summed EPSPs can carry the membrane up to firing level.
Occlusion
- Suppose presynaptic neuron A alone fires 5 postsynaptic neurons, and B alone fires another 5.
- Some neurons lie in a zone that A and B share. So when A and B fire together, only 8 neurons discharge, not 10. This shortfall is occlusion.
Draw it: occlusion
Draw two presynaptic neurons, A and B, each fanning out to its own group of five postsynaptic neurons. Overlap the two groups so that two neurons sit in the shared zone. Write the count beneath: A alone 5, B alone 5, A and B together 8.
- Worth knowing, though not in your pages: the opposite effect is seen when A and B each bring extra neurons only part-way to threshold (their subliminal fringe). Firing together, they then excite more neurons than the two do separately. This is how reflexes show facilitation; see Properties of spinal reflexes.
Habituation, sensitization and potentiation
- These change transmission with use: habituation weakens it, while sensitization and potentiation strengthen it.
| Change | Effect | Cause |
|---|---|---|
| Habituation | ↓ release with repetition | Ca²⁺ channels inactivated; fewer vesicles |
| Sensitization | ↑ response, short-lived | ↑ Ca²⁺ entry into the terminal |
| Post-tetanic potentiation | ↑ release after a burst | ↑ Ca²⁺ in the presynaptic knob |
| Long-term potentiation | ↑ transmission, long-lasting | ↑ Ca²⁺ in the postsynaptic cell, via NMDA |
- Habituation: transmitter release falls off gradually when impulses keep arriving. The likely cause is long-lasting inactivation of the knob’s Ca²⁺ channels, or a shortage of vesicles in the terminal.
- Sensitization: when transmission is paired with a painful or unpleasant sensation, the response grows larger and larger by presynaptic facilitation. It is short-lived, and is explained by more Ca²⁺ entering the presynaptic terminal.
- Potentiation is transmission that stays enhanced for a long time. It comes in two forms:
- post-tetanic potentiation (PTP), the shorter-lived: a train of stimuli leaves extra Ca²⁺ in the presynaptic knob, so more transmitter is released;
- long-term potentiation (LTP): Ca²⁺ rises in the postsynaptic neuron because NMDA (N-methyl-D-aspartate) channels open, glutamate for example opening them, and intracellular proteins increase.
PTP or LTP: which side of the synapse?
PTP is a presynaptic change: extra Ca²⁺ in the knob. LTP is a postsynaptic change: Ca²⁺ entering through NMDA channels. Mixing up the two sides is the usual mistake.
- Worth knowing, though not in your pages: LTP is best studied in the hippocampus, and it is taken as a cellular model of memory.
Synaptic plasticity
- Transmission at a synapse can be modified, both to suit the body’s needs and to learn the right response to a particular stimulus.
- The cells involved hold on to these changes for a variable time, and this is the basis of learning and memory.
- A long-term change of this kind in synapses is synaptic plasticity. Remodelling of dendritic spines is part of it (Synapses and synaptic transmission), and nitric oxide carries a signal back from the postsynaptic to the presynaptic neuron during it (Neurotransmitters).
- Worth knowing, though not in your pages: habituation, sensitization, PTP and LTP all count as forms of plasticity, and long-term depression (LTD) is the counterpart of LTP.
Exam-answer skeleton: "Describe the properties of synapses" (long essay)
- Define a synapse in one line, then list the properties.
- Law of forward conduction (and its exception); synaptic delay, 0.5 ms, and how it counts the synapses in a reflex arc.
- Divergence and convergence, with a diagram.
- EPSP and IPSP in a line each.
- Synaptic inhibition: direct (Golgi tendon organ via an interneuron), presynaptic (three mechanisms, GABA-A and GABA-B, baclofen), feedback (Renshaw cell, drawn) and feedforward (cerebellum).
- Facilitation and its mechanism; temporal and spatial summation; occlusion (5 + 5 gives 8).
- Habituation, sensitization, PTP and LTP.
- Close with synaptic plasticity as the basis of learning and memory.
Asked in exams
- Renshaw cell (recurrent) inhibition: Jul 2012, 2 marks · Aug 2024, MCQ