Metaplasticity

Metaplasticity is the plasticity of synaptic plasticity—the idea that the rules governing how synapses change strength are themselves modifiable by prior activity and neuromodulatory state. In other words, the capacity for long-term potentiation (LTP) or long-term depression (LTD) at a synapse can be shifted by previous neural activity, altering how future experiences produce synaptic change. The concept helps explain how neural networks remain flexible enough to learn new information while avoiding excessive instability.

Mechanisms underlying metaplasticity include shifts in the induction thresholds for LTP and LTD, changes in receptor composition and function, and alterations in intracellular signaling pathways. For example, changes in NMDA receptor subunit composition, phosphorylation status, or calcium dynamics can modulate calcium entry and downstream cascades that determine plastic outcomes. Neuromodulators such as acetylcholine, norepinephrine, and dopamine can set the brain’s plasticity state, enhancing or dampening synaptic modification during attention, arousal, or reward. Homeostatic processes, including synaptic scaling in response to global activity levels, also contribute by adjusting overall synaptic strength and thereby shaping subsequent Hebbian changes.

Regions often associated with metaplasticity include the hippocampus and the visual cortex, though the phenomenon is relevant across cortical and subcortical circuits. Metaplasticity is considered important for balanced learning and memory formation, enabling networks to encode new information without compromising stability. Alterations in metaplasticity have been discussed in the contexts of aging and neurological disorders such as Alzheimer's disease and schizophrenia.