title: Mechanisms of heterosynaptic metaplasticity.
abstract: Synaptic plasticity is fundamental to the neural processes underlying learning and memory. Interestingly, synaptic plasticity itself can be dynamically regulated by prior activity, in a process termed 'metaplasticity', which can be expressed both homosynaptically and heterosynaptically. Here, we focus on heterosynaptic metaplasticity, particularly long-range interactions between synapses spread across dendritic compartments, and review evidence for intracellular versus intercellular signalling pathways leading to this effect. Of particular interest is our previously reported finding that priming stimulation in stratum oriens of area CA1 in the hippocampal slice heterosynaptically inhibits subsequent long-term potentiation and facilitates long-term depression in stratum radiatum. As we have excluded the most likely intracellular signalling pathways that might mediate this long-range heterosynaptic effect, we consider the hypothesis that intercellular communication may be critically involved. This hypothesis is supported by the finding that extracellular ATP hydrolysis, and activation of adenosine A2 receptors are required to induce the metaplastic state. Moreover, delivery of the priming stimulation in stratum oriens elicited astrocytic calcium responses in stratum radiatum. Both the astrocytic responses and the metaplasticity were blocked by gap junction inhibitors. Taken together, these findings support a novel intercellular communication system, possibly involving astrocytes, being required for this type of heterosynaptic metaplasticity.
authors.affiliation: Department of Psychology and Brain Health Research Centre, University of Otago, , PO Box 56, Dunedin 9054, New Zealand.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Hulme
authors.forename: Owen D
authors.initials: OD
authors.lastname: Jones
authors.forename: Clarke R
authors.initials: CR
authors.lastname: Raymond
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sah
authors.forename: Wickliffe C
authors.initials: WC
authors.lastname: Abraham
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D006868:Hydrolysis; D007858:Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate
keywords: astrocytes; gap junctions; intercellular signalling; long-term depression; long-term potentiation; metaplasticity