title: Involvement of cannabinoid CB1 receptor in associative learning and in hippocampal CA3-CA1 synaptic plasticity.
abstract: We studied, in behaving mice, the contribution of CB1 receptors to the activity-dependent changes induced at the hippocampal CA3-CA1 synapse by associative learning and following experimentally evoked long-term potentiation (LTP). Mice were classically conditioned to evoke eyelid responses with a trace paradigm using a tone as conditioned stimulus (CS) and an electric shock as unconditioned stimulus (US). Field excitatory postsynaptic potentials (fEPSPs) were evoked at the CA3-CA1 synapse during the CS-US interval across training. Conditioning was performed in presence of an agonist (WIN55,212-2) alone or with an antagonist (AM251) of the CB1 receptor, injected either systemically or locally. Conditioned responses (CRs) and fEPSP potentiation were depressed by WIN55,212-2. LTP was evoked by high-frequency stimulation of Schaffer collaterals after systemic or local WIN55,212-2 and AM251 injections. WIN55,212-2 affected the induction phase of LTP, mainly when injected locally. The addition of AM251 canceled out the effects of WIN55,212-2. Similar experiments were carried out in animals lacking the CB1 receptor (CB1(-/-) mice) and following silencing of hippocampal CB1 receptors (CB1R-siRNA-injected animals). In this case, CRs (CB1(-/-) mice) and LTP (CB1(-/-) and CB1R-siRNA-injected mice) reached lower values than their respective controls. Results offer new insights for understanding CB1 receptor contribution to associative learning and to CA3-CA1 synaptic plasticity.
authors.affiliation: División de Neurociencias, Universidad Pablo de Olavide, Sevilla.
authors.forename: Noelia
authors.initials: N
authors.lastname: Madroñal
authors.forename: Agnès
authors.initials: A
authors.lastname: Gruart
authors.forename: Olga
authors.initials: O
authors.lastname: Valverde
authors.forename: Isabel
authors.initials: I
authors.lastname: Espadas
authors.forename: Rosario
authors.initials: R
authors.lastname: Moratalla
authors.forename: José M
authors.initials: JM
authors.lastname: Delgado-García
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000502:physiology*; D056654:CA3 Region, Hippocampal / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000172:deficiency / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*
chemical_list: D043884:Receptor, Cannabinoid, CB1