Short-Term and Long-Term Synaptic Plasticity

Synapses are not fixed: their strength changes with use. Short-term plasticity alters transmission over milliseconds to minutes, mostly through changes in the probability of transmitter release, while long-term plasticity produces lasting strengthening (long-term potentiation) or weakening (long-term depression) of synapses, widely regarded as a cellular substrate of learning and memory. This topic introduces both timescales and their mechanisms.

Definition

Synaptic plasticity is the activity-dependent modification of synaptic strength, encompassing short-term changes in release probability lasting milliseconds to minutes and long-term potentiation or depression that can persist for hours or longer and is considered a basis for learning and memory.

Scope

This topic covers activity-dependent changes in synaptic strength: short-term facilitation and depression, long-term potentiation and depression, spike-timing dependence, and homeostatic scaling that keeps activity within bounds. It is framed as physiology and does not provide clinical or treatment guidance.

Core questions

• How does prior activity change the strength of a synapse?
• What distinguishes short-term from long-term plasticity mechanistically?
• How do long-term potentiation and depression arise at the same synapse?
• How do neurons keep their overall activity within a stable range?

Key concepts

• Short-term facilitation and depression
• Paired-pulse effects
• Long-term potentiation (LTP)
• Long-term depression (LTD)
• NMDA-receptor-dependent plasticity
• Spike-timing-dependent plasticity
• Homeostatic synaptic scaling
• Plasticity as a memory substrate

Key theories

Hebbian plasticity and long-term potentiation

Synapses that are repeatedly active when the postsynaptic cell is also active become strengthened; in the hippocampus this is realised as NMDA-receptor-dependent long-term potentiation, proposed as a synaptic model of memory.

Spike-timing-dependent plasticity

The sign and size of long-term change depend on the millisecond timing between presynaptic and postsynaptic spikes, providing a temporally precise Hebbian learning rule.

Homeostatic synaptic scaling

Neurons globally adjust the strength of their synapses to counteract prolonged increases or decreases in activity, stabilising firing while preserving relative synaptic weights.

Mechanisms

Short-term plasticity arises largely from changes in presynaptic calcium and the availability of releasable vesicles: residual calcium can facilitate release, while depletion of the readily releasable pool can depress it over short intervals. Long-term potentiation at many central synapses depends on the NMDA receptor, which admits calcium only when the postsynaptic cell is depolarised at the same time the synapse is active; the resulting calcium signal triggers signalling cascades that increase synaptic strength, often by adding AMPA receptors, whereas different patterns of calcium entry can instead produce long-term depression. The timing of pre- and postsynaptic spikes shapes the direction of these changes, and separate homeostatic mechanisms scale synaptic weights up or down to keep overall neuronal activity stable.

Clinical relevance

Synaptic plasticity is studied as a substrate of learning and memory and as a process disturbed in conditions affecting cognition, and the molecules that mediate it are of interest as targets for understanding such disorders. This entry describes the underlying physiology and is offered as reference background rather than as diagnostic or treatment advice.

History

Long-term potentiation was first described in the hippocampus in the early 1970s and developed over the following decades into a leading cellular model of memory, reviewed influentially by Bliss and Collingridge in 1993. Parallel work characterised short-term plasticity, spike-timing dependence, and homeostatic scaling, broadening the account of how synaptic strength is regulated across timescales.

Key figures

• Timothy Bliss
• Graham Collingridge
• Eric Kandel
• Gina Turrigiano

Seminal works

• bliss-collingridge-1993
• zucker-regehr-2002
• kandel-2001

Frequently asked questions

What is long-term potentiation?

It is a lasting increase in synaptic strength that follows certain patterns of activity, often dependent on the NMDA receptor and the calcium signal it admits, and it is widely regarded as a cellular model of memory.

How does short-term plasticity differ from long-term plasticity?

Short-term plasticity changes transmission over milliseconds to minutes, mainly through presynaptic changes in release probability, whereas long-term plasticity produces persistent strengthening or weakening that involves lasting molecular and structural changes.