RT Journal Article
SR Electronic
T1 Interaction of Calcineurin and Type-A GABA Receptor γ<sub>2</sub> Subunits Produces Long-Term Depression at CA1 Inhibitory Synapses
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 826
OP 836
DO 10.1523/JNEUROSCI.23-03-00826.2003
VO 23
IS 3
A1 Wang, Jian
A1 Liu, ShuHong
A1 Haditsch, Ursula
A1 Tu, WeiHong
A1 Cochrane, Kimberley
A1 Ahmadian, Gholamreza
A1 Tran, Linda
A1 Paw, Jadine
A1 Wang, YuTian
A1 Mansuy, Isabelle
A1 Salter, Michael M.
A1 Lu, YouMing
YR 2003
UL http://www.jneurosci.org/content/23/3/826.abstract
AB 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 (GABAARs) via the direct binding of CaN catalytic domain to the second intracellular domain of the GABAAR-γ2subunits. Prevention of the CaN–GABAA 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 GABAA receptors is both necessary and sufficient for inducing LTD at CA1 individual inhibitory synapses.