A novel postsynaptic mechanism for heterosynaptic sharing of short-term plasticity

Postsynaptic release of Ca²⁺ from intracellular stores is an important means of cellular signaling that mediates numerous forms of synaptic plasticity. Previous studies have identified a postsynaptic intracellular Ca²⁺ requirement for a form of short-term plasticity, post-tetanic potentiation (PTP) at sensory neuron (SN) - motor neuron synapses in Aplysia. Here, we show that postsynaptic IP₃-mediated Ca²⁺ release in response to a presynaptic tetanus in an SN that induces PTP can confer transient plasticity onto a neighboring SN synapse receiving subthreshold activation. This heterosynaptic sharing of plasticity represents a dynamic, short-term synaptic enhancement of synaptic inputs onto a common postsynaptic target. Heterosynaptic sharing is blocked by postsynaptic disruption of Ca ²⁺- and IP₃-mediated signaling, and, conversely, it is mimicked by postsynaptic injection of nonhydrolyzable IP₃ , and by photolysis of caged IP₃ in the MN. The molecular mechanism for heterosynaptic sharing involves metabotropic glutamate receptors and Homerdependent interactions, indicating that Homer can facilitate the integration of Ca²⁺-dependent plasticity at neighboring postsynaptic sites and provides a postsynaptic mechanism for the spread of plasticity induced by presynaptic activation. Our results support a model in which postsynaptic summation of IP₃ signals from suprathreshold and subthreshold inputs results in molecular coincidence detection that gives rise to a novel form of heterosynaptic plasticity. Copyright