title: A novel postsynaptic mechanism for heterosynaptic sharing of short-term plasticity.
abstract: Postsynaptic release of Ca(2+) from intracellular stores is an important means of cellular signaling that mediates numerous forms of synaptic plasticity. Previous studies have identified a postsynaptic intracellular Ca(2+) 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 IP(3)-mediated Ca(2+) 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 IP(3)-mediated signaling, and, conversely, it is mimicked by postsynaptic injection of nonhydrolyzable IP(3), and by photolysis of caged IP(3) in the MN. The molecular mechanism for heterosynaptic sharing involves metabotropic glutamate receptors and Homer-dependent interactions, indicating that Homer can facilitate the integration of Ca(2+)-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 IP(3) signals from suprathreshold and subthreshold inputs results in molecular coincidence detection that gives rise to a novel form of heterosynaptic plasticity.
authors.affiliation: Department of Neurobiology and Behavior and Center for the Neurobiology of Learning and Memory, University of California, Irvine, California 92697, USA.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Reissner
authors.forename: Lu
authors.initials: L
authors.lastname: Pu
authors.forename: Joanna H
authors.initials: JH
authors.lastname: Schaffhausen
authors.forename: Heather D
authors.initials: HD
authors.lastname: Boyle
authors.forename: Ian F
authors.initials: IF
authors.lastname: Smith
authors.forename: Ian
authors.initials: I
authors.lastname: Parker
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carew
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D017952:Ganglia, Invertebrate / Q000187:drug effects / Q000502:physiology; D000072233:Homer Scaffolding Proteins; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018094:Receptors, Metabotropic Glutamate; D002118:Calcium