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The Journal of Neurophysiology Vol. 85 No. 1 January 2001, pp. 425-434
Copyright ©2001 by the American Physiological Society
Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520
Gao, Xiao-Bing and
Anthony N. Van Den Pol.
GABA, Not Glutamate, a Primary Transmitter Driving Action
Potentials in Developing Hypothalamic Neurons. J. Neurophysiol. 85: 425-434, 2001. Neuronal
activity is critical for many aspects of brain development. It has
often been assumed that the primary excitatory transmitter driving this
activity is glutamate. In contrast, we report that during early
development, synaptic release of GABA, the primary inhibitory
neurotransmitter in the mature brain, is not only excitatory but in
addition plays a more robust role than glutamate in generating spike
activity in mouse hypothalamic neurons. Based on gramicidin perforated
whole cell and extracellular recording, which leave intracellular
Cl
unperturbed in brain slices and cultures,
the GABAA receptor antagonist bicuculline induced
a dramatic decrease in spike frequency (83% decrease) in developing
neurons, three times greater than that generated by glutamate receptor
antagonists 2-amino-5-phosphono-pentanoic acid and
6-cyano-7-nitroquinoxalene-2,3-dione. Thus a number of factors related
to spike-dependent stabilization of neuronal connections, including
Hebbian mechanisms, that are generally applied to glutamate transmission may also participate in stabilization of GABA circuits.
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