Questions: Short-Term Synaptic Plasticity: Facilitation and Depression

Question 1

A facilitating synapse receives two action potentials separated by 20 ms. Why does the second action potential typically trigger a larger postsynaptic response than the first?

• A. The postsynaptic membrane inserts additional receptors during the 20 ms interval
• B. The second action potential propagates faster because the axon is already partially depolarized
• C. Residual calcium from the first action potential adds to the calcium influx triggered by the second, increasing vesicle release probability
• D. The presynaptic terminal synthesizes and docks new vesicles in the 20 ms between stimuli

Answer: (C)

Facilitation operates through residual calcium. After the first action potential, calcium pumps and buffers clear Ca²⁺ from the terminal, but not instantaneously — a residual signal persists for tens of milliseconds. When the second spike arrives during this window, its Ca²⁺ influx adds to the residual, producing a higher peak concentration. Because vesicle fusion probability is a steep nonlinear function of calcium (roughly proportional to Ca²⁺ to the fourth power), even a modest residual boost causes a dramatically larger release. Options A and D describe processes that operate on much longer timescales.

Question 2

A sensory circuit uses a depressing synapse to encode the onset of a stimulus rather than its sustained duration. This strategy works because:

• A. Depression strengthens the synapse during continuous stimulation, amplifying sustained signals
• B. The depressing synapse has an exceptionally large readily-releasable vesicle pool that sustains transmission indefinitely
• C. Depression attenuates responses to sustained input, so only the onset — a change from silence — produces a strong response
• D. Postsynaptic receptor desensitization enhances the response during continuous stimulation

Answer: (C)

A depressing synapse acts as a change detector or novelty filter. Rapid vesicle depletion means that each successive stimulus in a train draws from an increasingly depleted pool, producing progressively smaller postsynaptic currents. A constant stimulus therefore generates a declining neural response — adaptation. The circuit fires strongly to the onset (the transition from no stimulus to stimulus) but signals very little during sustained input. This is exploited in auditory circuits to encode onset timing with high precision rather than tracking steady-state sounds.

Question 3

Short-term synaptic plasticity refers to changes in synaptic strength that persist for hours or days after high-frequency activity, similar to long-term potentiation (LTP).

• T. True
• F. False

Answer: False

False. Short-term plasticity operates on timescales of approximately 100 milliseconds to a few seconds — far shorter than LTP or LTD, which last hours to a lifetime. Short-term plasticity is also mechanistically distinct: it relies on presynaptic calcium dynamics and vesicle pool depletion, not on the protein synthesis and receptor trafficking that underlie long-term changes. The defining feature of short-term plasticity is that it is transient and reverses naturally as calcium is cleared and vesicle pools refill.

Question 4

A facilitating synapse acts as a high-pass filter because it responds weakly to isolated, low-frequency inputs but strongly to high-frequency bursts of activity.

• T. True
• F. False

Answer: True

True. At low firing frequencies, calcium is fully cleared between spikes, so each action potential encounters the same baseline release probability — low, because the initial release probability at facilitating synapses is typically low. At high frequencies, residual calcium accumulates faster than it is cleared, progressively boosting release probability with each spike in the burst. The synapse is therefore selective for high-frequency information — it 'passes' bursts while attenuating sparse, low-rate activity, exactly the behavior of a high-pass filter.

Question 5

Explain how synaptic depression transforms a synapse into a 'novelty detector,' and why this is useful for sensory processing.

Model answer: A depressing synapse depletes its readily-releasable vesicle pool during sustained stimulation, so each successive release event draws from a smaller pool and produces a weaker postsynaptic response. A continuous sensory input therefore drives progressively diminishing neural responses — the circuit adapts. Only a change in the stimulus (onset, offset, or shift in intensity) replenishes relative vesicle availability and generates a strong response. This makes depressing synapses useful for detecting transitions and novelty rather than tracking steady background signals.

This temporal filtering function is exploited widely in sensory systems. In the auditory brainstem, depression at the calyx of Held synapse sharpens onset responses used for sound localization. In visual cortex, adaptation suppresses responses to static stimuli while preserving sensitivity to moving or changing inputs. The key insight is that synaptic strength is not fixed — it encodes the history of recent activity, making the synapse an active participant in signal processing rather than a passive relay.