heterosynaptic

Heterosynaptic plasticity is an activity-dependent change in synaptic strength that occurs at synapses not directly stimulated by a given input. This contrasts with homosynaptic plasticity, in which changes are restricted to the activated synapses. Heterosynaptic changes have been observed in several CNS regions, including the hippocampus and cerebral cortex, and in various forms of plasticity such as long-term potentiation (LTP) and long-term depression (LTD). In experiments, a robust induction at one set of synapses on a neuron can be followed by potentiation or depression at neighboring, nonstimulated synapses on the same cell.

The underlying mechanisms are not fully resolved, but involve intercellular signaling that spreads beyond the stimulated synapse. Candidates include diffusion of signaling molecules such as nitric oxide and endocannabinoids; spillover of neurotransmitters; neuromodulators (e.g., norepinephrine, acetylcholine) that alter excitability and plasticity thresholds; and astrocyte-mediated signaling or intracellular calcium waves. Through these pathways, the activity at one input can alter the synaptic strength at other inputs by altering postsynaptic receptor availability, presynaptic release probability, or local metabolic state.

Heterosynaptic plasticity is thought to contribute to synaptic competition and homeostatic regulation, helping to normalize overall input strength, prevent runaway excitation, and shape circuit development and learning by coordinating changes across multiple synaptic contacts on a single neuron.