title: Interaction of calcineurin and type-A GABA receptor gamma 2 subunits produces long-term depression at CA1 inhibitory synapses.
abstract: Long-term depression (LTD) is an activity-dependent weakening of synaptic efficacy at individual inhibitory synapses, a possible cellular model of learning and memory. Here, we show that the induction of LTD of inhibitory transmission recruits activated calcineurin (CaN) to dephosphorylate type-A GABA receptor (GABA(A)Rs) via the direct binding of CaN catalytic domain to the second intracellular domain of the GABA(A)R-gamma(2) subunits. Prevention of the CaN-GABA(A) receptor complex formation by expression of an autoinhibitory domain of CaN in the hippocampus of transgenic mice blocks the induction of LTD. Conversely, genetic expression of the CaN catalytic domain in the hippocampus depresses inhibitory synaptic responses, occluding LTD. Thus, an activity-dependent physical and functional interaction between CaN and GABA(A) receptors is both necessary and sufficient for inducing LTD at CA1 individual inhibitory synapses.
authors.affiliation: Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Canada, T2N 4N1.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: ShuHong
authors.initials: S
authors.lastname: Liu
authors.forename: Ursula
authors.initials: U
authors.lastname: Haditsch
authors.forename: WeiHong
authors.initials: W
authors.lastname: Tu
authors.forename: Kimberley
authors.initials: K
authors.lastname: Cochrane
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Ahmadian
authors.forename: Linda
authors.initials: L
authors.lastname: Tran
authors.forename: Jadine
authors.initials: J
authors.lastname: Paw
authors.forename: YuTian
authors.initials: Y
authors.lastname: Wang
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mansuy
authors.forename: Michael M
authors.initials: MM
authors.lastname: Salter
authors.forename: You Ming
authors.initials: YM
authors.lastname: Lu
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D046911:Macromolecular Substances; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
chemical_list: C546280:Gabrg2 protein, mouse; D046911:Macromolecular Substances; D021122:Protein Subunits; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D019703:Calcineurin