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.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OOU.#10393/23518 |
| Date | 19 November 2012 |
| Creators | Kesner, Philip |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thèse / Thesis |
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