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The Journal of Neuroscience, September 16, 2009, 29(37):11650-11661; doi:10.1523/JNEUROSCI.3587-09.2009

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Development/Plasticity/Repair
GABA_B Receptor Activation Triggers BDNF Release and Promotes the Maturation of GABAergic Synapses

Hervé Fiorentino,¹ Nicola Kuczewski,¹ Diabe Diabira,¹ Nadine Ferrand,¹ Menelas N. Pangalos,² Christophe Porcher,¹ and Jean-Luc Gaiarsa¹

¹Institut de Neurobiologie de la Méditerranée, Inserm (Institut National de la Santé et de la Recherche Médicale), Unité 901, and Université de La Méditerranée, 13273 Marseille Cedex 09, France, and ²Wyeth Research, Discovery Research Neurosciences, Monmouth Junction, New Jersey 08852

Correspondence should be addressed to Jean-Luc Gaiarsa, Institut de Neurobiologie de la Méditerranée, Parc scientifique de Luminy, BP 13, 13273 Marseille Cedex 09, France. Email: gaiarsa{at}inmed.univ-mrs.fr

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.

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Received July 24, 2009; accepted Aug. 8, 2009.

Correspondence should be addressed to Jean-Luc Gaiarsa, Institut de Neurobiologie de la Méditerranée, Parc scientifique de Luminy, BP 13, 13273 Marseille Cedex 09, France. Email: gaiarsa{at}inmed.univ-mrs.fr

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