title: Purinergic receptor- and gap junction-mediated intercellular signalling as a mechanism of heterosynaptic metaplasticity.
abstract: Synaptic plasticity is subject to activity-dependent long-term modification (metaplasticity). We have recently described a novel form of heterosynaptic metaplasticity in hippocampal CA1, whereby 'priming' activity at one set of synapses confers a metaplastic state that inhibits subsequent LTP both within and between dendritic compartments. Here, we investigated the roles of purinergic signalling and gap junctions in mediating this long-distance communication between synapses. We found that the heterosynaptic metaplasticity requires the hydrolysis of extracellular ATP to adenosine, and activation of adenosine A2, but not A1 receptors. The metaplasticity was also blocked by the non-selective gap junction blockers carbenoxolone and meclofenamic acid, and by a connexin43-specific mimetic peptide. These results indicate that an intercellular signalling cascade underlies the long-distance communication required for this form of metaplasticity.
authors.affiliation: Department of Psychology and Brain Health Research Centre, University of Otago, Box 56, Dunedin 9054, New Zealand. Electronic address: owen.jones@otago.ac.nz.
authors.forename: Owen D
authors.initials: OD
authors.lastname: Jones
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Hulme
authors.forename: Wickliffe C
authors.initials: WC
authors.lastname: Abraham
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D002450:Cell Communication; D004558:Electric Stimulation; D017629:Gap Junctions / Q000378:metabolism*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation; D008297:Male; D009473:Neuronal Plasticity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000378:metabolism*
chemical_list: D011983:Receptors, Purinergic
keywords: Adenosine receptors; Gap junctions; Hippocampus; Long-term potentiation; Priming