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Brain-derived neurotrophic factor modulates fast synaptic inhibition by regulating GABA(A) receptor phosphorylation, activity, and cell-surface stability

Jovanovic, JN; Thomas, P; Kittler, JT; Smart, TG; Moss, SJ; (2004) Brain-derived neurotrophic factor modulates fast synaptic inhibition by regulating GABA(A) receptor phosphorylation, activity, and cell-surface stability. J NEUROSCI , 24 (2) 522 - 530. 10.1523/JNEUROSCI.3606-03.2004. Green open access

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Abstract

The efficacy of GABAergic synaptic inhibition is a principal factor in controlling neuronal activity. We demonstrate here that brain-derived neurotrophic factor modulates the activity of GABA(A) receptors, the main sites of fast synaptic inhibition in the brain, within minutes of application. Temporally, this comprised an early enhancement in the miniature IPSC amplitude, followed by a prolonged depression. This modulation was concurrent with enhanced PKC-mediated phosphorylation, followed by protein phosphatase 2A (PP2A)-mediated dephosphorylation of the GABA(A) receptor. Mechanistically, these events were facilitated by differential recruitment of PKC, receptor for activated C-kinase, and PP2A to GABA(A) receptors, depending on the phosphorylation state of the receptor beta(3)-subunit. Thus, transient formation of GABA(A) receptor signaling complexes has the potential to provide a basis for acute changes in receptor function underlying GABAergic synaptic plasticity.

Type: Article
Title: Brain-derived neurotrophic factor modulates fast synaptic inhibition by regulating GABA(A) receptor phosphorylation, activity, and cell-surface stability
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.3606-03.2004
Publisher version: http://dx.doi.org/10.1523/JNEUROSCI.3606-03.2004
Language: English
Additional information: This work is available to the public to copy, distribute, or display under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license.
Keywords: GABA, growth factor, phosphatase, phosphorylation, protein kinase, synaptic, PROTEIN-KINASE-C, A RECEPTOR, INTRACELLULAR DOMAINS, FUNCTIONAL MODULATION, CORTICAL-NEURONS, AMPA RECEPTORS, BETA SUBUNITS, ION CHANNELS, FACTOR BDNF, RAT-BRAIN
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/122668
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