Acute Cannabinoid Treatment 'in vivo' Causes an Astroglial CB1R-Dependent LTD At Excitatory CA3-CA1 Synapses Involving NMDARs and Protein Synthesis

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Title: Acute Cannabinoid Treatment 'in vivo' Causes an Astroglial CB1R-Dependent LTD At Excitatory CA3-CA1 Synapses Involving NMDARs and Protein Synthesis
Authors: Kesner, Philip
Date: 2012
Abstract: Cannabinoids have been shown to alter synaptic plasticity but the mechanism by which this occurs at hippocampal CA3-CA1 synapses in vivo is not yet known. Utilizing in vivo electrophysiological recordings of field excitatory postsynaptic potentials (fEPSP) on anesthetized rats and mice as well as three lines of conditional knockout mouse models, the objective was to show a two-part mechanistic breakdown of cannabinoid-evoked CA3-CA1 long-term depression (LTD) in its induction as well as early and later-phase expression stages. It was determined that this cannabinoid-induced in vivo LTD requires cannabinoid type-1 receptors (CB1Rs) on astrocytes, but not CB1Rs on glutamatergic or GABAergic neuronal axons/terminals. Pharmacological testing determined that cannabinoid-induced in vivo LTD also requires activation of NMDA receptors (NMDAR) and subsequent postsynaptic endocytosis of AMPA receptors (AMPAR). There exists a clear role for NR2B-containing NMDARs in a persistent, transitory form, potentially related to prolonged or delayed glutamate release (possibly as a result of the astrocytic network). A key determination of the expression phase is the involvement of new protein synthesis (using translation and transcription inhibitors) – further evidence of the long-term action of the synaptic plasticity from a single cannabinoid dose.
URL: http://hdl.handle.net/10393/23518
http://dx.doi.org/10.20381/ruor-6210
CollectionThèses, 2011 - // Theses, 2011 -
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