KCC2 Gates Activity-Driven AMPA Receptor Traffic through Cofilin Phosphorylation

• DOI: 10.1523/jneurosci.1735-15.2015
• Publication Date: 2015-12-02T17:22:23Z
• Authors: Quentin Chevy; Martin Heubl; Marie Goutierre; Stéphanie Backer; Imane Moutkine; Emmanuel Eugène; Evelyne Bloch-Gal...; Sabine Lévi; Jean Christophe P...
• Keywords: Cofilin; Silent synapse

Expression of the neuronal K/Cl transporter KCC2 is tightly regulated throughout development and by both normal pathological activity. Changes in expression have often been associated with altered chloride homeostasis GABA signaling. However, recent evidence supports a role function glutamatergic synapses through mechanisms that remain poorly understood. Here we show suppressing rat hippocampal neurons precludes long-term potentiation specifically preventing activity-driven membrane delivery AMPA receptors. This effect independent can be accounted for increased Rac1/PAK- LIMK-dependent cofilin phosphorylation actin polymerization dendritic spines. Our results demonstrate plays critical regulation spine cytoskeleton gates plasticity at excitatory cortical neurons. SIGNIFICANCE STATEMENT transporters, such as KCC2, occur during postnatal are induced variety neurological psychiatric conditions. Such changes expected to primarily impact signaling because GABAA receptors predominantly permeable ions. forms clusters near interacts several actin-related proteins. We strictly required LTP synapses. due interaction Rac1/PAK pathway controls polymerization. Suppressing this promotes thereby hindering receptor traffic upon suppression. Alterations therefore not only GABAergic but also synaptic long term plasticity.