Purinergic receptor- and gap junction-mediated intercellular signalling as a mechanism of heterosynaptic metaplasticity

• Published in: Neurobiology of learning and memory Vol. 105; pp. 31 - 39
• Main Authors: Jones, Owen D., Hulme, Sarah R., Abraham, Wickliffe C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.10.2013; Elsevier; Elsevier BV
• Subjects: Adenosine receptors; Animals; Behavioral psychophysiology; Biological and medical sciences; Brain; CA1 Region, Hippocampal - physiology; Cell Communication; Electric Stimulation; Fundamental and applied biological sciences. Psychology; Gap junctions; Gap Junctions - metabolism; Hippocampus; In Vitro Techniques; Long-Term Potentiation; Male; Neurobiology; Neuronal Plasticity; Priming; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Sprague-Dawley; Receptors, Purinergic - metabolism; Signal transduction; Priming; Adenosine receptors; Gap junctions; Long-term potentiation; Hippocampus; Priming effect; Central nervous system; Cell junction; Long term potentiation; Gap junction; Encephalon; Purinergic receptor; Synaptic plasticity; Adenosine receptor
• ISSN: 1074-7427; 1095-9564; 1095-9564
• DOI: 10.1016/j.nlm.2013.05.010

•Tetanisation of one input in area CA1 inhibits subsequent LTP on a second input.•This heterosynaptic metaplasticity extends within and across dendritic compartments.•The effect is robust across priming protocols, age groups and rodent species.•The effect requires hydrolysis of ATP, and activation of A2, but not A1 receptors.•Block by gap junction inhibitors suggests intercellular communication is required. 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.