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The Journal of Neuroscience, November 1, 2000, 20(21):8087-8095
Neuronal Activity and Brain-Derived Neurotrophic Factor
Regulate the Density of Inhibitory Synapses in Organotypic Slice
Cultures of Postnatal Hippocampus
Serge
Marty,
Rosine
Wehrlé, and
Constantino
Sotelo
Institut National de la Santé et de la Recherche
Médicale U106, Hôpital de la Salpêtrière,
Pavillon de l'Enfance et de l'Adolescence, 75651 Paris cedex 13, France
Hippocampal interneurons inhibit pyramidal neurons through the
release of the neurotransmitter GABA. Given the importance of
this inhibition for the proper functioning of the hippocampus, the
development of inhibitory synapses must be tightly regulated. In this
study, the possibility that neuronal activity and neurotrophins regulate the density of GABAergic inhibitory synapses was investigated in organotypic slice cultures taken from postnatal day 7 rats.
In hippocampal slices cultured for 13 d in the presence of the
GABAA receptor antagonist bicuculline, the density of
glutamic acid decarboxylase (GAD) 65-immunoreactive terminals was
increased in the CA1 area when compared with control slices. Treatment
with the glutamate receptor antagonist
6,7-dinitroquinoxaline-2,3-dione decreased the density of
GAD65-immunoreactive terminals in the stratum oriens of CA1. These
treatments had parallel effects on the density of GABA-immunoreactive
processes. Electron microscopic analysis after postembedding immunogold
labeling with antibodies against GABA indicated that bicuculline
treatment increased the density of inhibitory but not excitatory
synapses. Application of exogenous BDNF partly mimicked the stimulatory
effect of bicuculline on GAD65-immunoreactive terminals. Finally,
antibodies against BDNF, but not antibodies against nerve growth
factor, decrease the density of GAD65-immunoreactive terminals in
bicuculline-treated slices.
Thus, neuronal activity regulates the density of inhibitory synapses
made by postnatal hippocampal interneurons, and BDNF could mediate part
of this regulation. This regulation of the density of inhibitory
synapses could represent a feedback mechanism aimed at maintaining an
appropriate level of activity in the developing hippocampal networks.
Key words:
rat; development; Ammon's horn; GABAergic neurons; interneurons; neurotrophins
Copyright © 2000 Society for Neuroscience 0270-6474/00/20218087-09$05.00/0
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