title: GABA autoreceptors regulate the induction of LTP.
abstract: Understanding the mechanisms involved in long-term potentiation (LTP) should provide insights into the cellular and molecular basis of learning and memory in vertebrates. It has been established that in the CA1 region of the hippocampus the induction of LTP requires the transient activation of the N-methyl-D-aspartate (NMDA) receptor system. During low-frequency transmission, significant activation of this system is prevented by gamma-aminobutyric acid (GABA) mediated synaptic inhibition which hyperpolarizes neurons into a region where NMDA receptor-operated channels are substantially blocked by Mg2+ (refs. 5, 6). But during high-frequency transmission, mechanisms are evoked that provide sufficient depolarization of the postsynaptic membrane to reduce this block and thereby permit the induction of LTP. We now report that this critical depolarization is enabled because during high-frequency transmission GABA depresses its own release by an action on GABAB autoreceptors, which permits sufficient NMDA receptor activation for the induction of LTP. These findings demonstrate a role for GABAB receptors in synaptic plasticity.
authors.affiliation: Department of Pharmacology, School of Medical Sciences, University of Bristol, UK.
authors.forename: C H
authors.initials: CH
authors.lastname: Davies
authors.forename: S J
authors.initials: SJ
authors.lastname: Starkey
authors.forename: M F
authors.initials: MF
authors.lastname: Pozza
authors.forename: G L
authors.initials: GL
authors.lastname: Collingridge
mesh_terms: D015762:2-Chloroadenosine / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009473:Neuronal Plasticity; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D015762:2-Chloroadenosine; C066430:CGP 35348; D002217:Carbachol; D001418:Baclofen