GABA(B) receptor activation triggers BDNF release and promotes the maturation of GABAergic synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] Journal article

Title	GABA(B) receptor activation triggers BDNF release and promotes the maturation of GABAergic synapses.
Author(s)	Fiorentino H, Kuczewski N, Diabira D, Ferrand N, Pangalos MN, Porcher C, Gaiarsa JL
Institution	Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale, Unité 901, and Université de La Méditerranée, 13273 Marseille Cedex 09, France.
Source	J Neurosci 2009 Sep 16; 29(37):11650-61.
MeSH	Animals Animals, Newborn Brain-Derived Neurotrophic Factor CREB-Binding Protein Cells, Cultured Enzyme-Linked Immunosorbent Assay Excitatory Amino Acid Antagonists Female GABA Antagonists Green Fluorescent Proteins Hippocampus Lysine Membrane Potentials Mice Mice, Knockout Neurons Patch-Clamp Techniques Phosphinic Acids Propanolamines Quinoxalines Receptors, GABA-B Sodium Channel Blockers Synapses Tetrodotoxin Valine gamma-Aminobutyric Acid
Abstract	GABA, the main inhibitory neurotransmitter in the adult brain, has recently emerged as an important signal in network development. Most of the trophic functions of GABA have been attributed to depolarization of the embryonic and neonatal neurons via the activation of ionotropic GABA(A) receptors. Here we demonstrate a novel mechanism by which endogenous GABA selectively regulates the development of GABAergic synapses in the developing brain. Using whole-cell patch-clamp recordings on newborn mouse hippocampi lacking functional GABA(B) receptors (GABA(B)-Rs) and time-lapse fluorescence imaging on cultured hippocampal neurons expressing GFP-tagged brain-derived neurotrophic factor (BDNF), we found that activation of metabotropic GABA(B) receptors (GABA(B)-Rs) triggers secretion of BDNF and promotes the development of perisomatic GABAergic synapses in the newborn mouse hippocampus. Because activation of GABA(B)-Rs occurs during the characteristic ongoing physiological network-driven synaptic activity present in the developing hippocampus, our results reveal a new mechanism by which synaptic activity can modulate the development of local GABAergic synaptic connections in the developing brain.
Language	eng
Pub Type(s)	Journal Article Research Support, Non-U.S. Gov't
PubMed ID	19759312

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