title: Coupling between GABA-A receptor and chloride transporter underlies ionic plasticity in cerebellar Purkinje neurons.
abstract: Ionic plasticity, a form of synaptic plasticity unique to inhibitory neurotransmission, can be induced in cerebellar Purkinje neurons by brain-derived neurotrophic factor (BDNF). It is expressed as a decrease in synaptic strength of GABA-A transmission onto Purkinje neurons due to reduced transmembrane chloride gradient. By making whole-cell recordings, we found that the effect of BDNF is mediated by neuronal potassium and chloride transporter KCC2 because it is blocked by inhibitors of KCC2 or by raising the intracellular chloride concentration. Under these conditions in which KCC2 activity is reduced, BDNF augments evoked GABA-A currents suggesting a direct facilitatory effect of BDNF on GABA-A receptor. We also found that the effect of BDNF is highly localized at the GABA-A synapse and is secured by physical coupling between GABA-A receptor and KCC2, as revealed by coimmunoprecipitation studies. Based on these results, we hypothesize that the interaction between KCC2 and specific subunit of GABA-A receptor represents a fundamental mechanism rendering the rapid induction of ionic plasticity in individual or input-specific GABA synapses possible. Such a mechanism may be important for the function of Purkinje neurons that are known to express GABA-A receptors with different subunit compositions.
authors: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Ying
authors: Y
authors: Huang
authors: Jian-Jun
authors: JJ
authors: Wang
authors: Wing-Ho
authors: WH
authors: Yung
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000166:cytology*; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D011963:Receptors, GABA-A; D027981:Symporters; D000096922:K Cl- Cotransporters