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J Neurophysiol 79: 716-726, 1998;
0022-3077/98 $5.00
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The Journal of Neurophysiology Vol. 79 No. 2 February 1998, pp. 716-726
Copyright ©1998 The American Physiological Society

GABA-Dependent Firing of Glutamate-Evoked Action Potentials at AMPA/Kainate Receptors in Developing Hypothalamic Neurons

Xiao-Bing Gao, Gong Chen, and Anthony N. van den Pol

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520

Gao, Xiao-Bing, Gong Chen, and Anthony N. van den Pol. GABA-dependent firing of glutamate-evoked action potentials at AMPA/kainate receptors in developing hypothalamic neurons. J. Neurophysiol. 79: 716-726, 1998. Although it plays a major inhibitory role in the adult mammalian CNS, gamma -aminobutyric acid (GABA) may have an excitatory function in developing neurons. The present study focuses on the dependence of glutamate on GABA to generate action potentials in developing hypothalamic neurons. Under conditions where glutamate by itself could not evoke an action potential, GABA facilitated glutamate-mediated depolarization to fire action potentials. This facilitation had a broad time window during the decaying phase of the GABA-mediated depolarization in developing neurons in culture. The glutamate-mediated depolarization was shunted only during the peak of GABA-mediated depolarization, but was facilitated after that.Similar results were obtained in the presence of 2-amino-5-phosphonopentanoic acid (AP5), indicating that GABA can facilitate glutamate responses independent of relief of the Mg2+ block of the N-methyl-D-aspartate (NMDA) receptor. This novel interaction between GABA- and glutamate-mediated excitation could play a role in strengthening neuronal circuits during early development and would exert a maximal effect if GABA and glutamate receptors were activated after a slight temporal delay.




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