Excitatory action of GABA in the terminal nerve gonadotropin-releasing hormone neurons.
The terminal nerve (TN)-gonadotropin-releasing hormone (GnRH) neurons have been suggested to function as a neuromodulatory system that regulates the motivational and arousal state of the animal and have served as a model system for the study of GnRH neuron physiology. To investigate the synaptic control of the TN-GnRH neurons, we analyzed electrophysiologically the effect of GABA on the TN-GnRH neurons. GABA generally hyperpolarizes most of the neurons in the adult brain by activating GABA(A) receptors while the activation of GABA(A) receptors depolarizes some specific neurons in the mature brain. Here we examined the GABA(A) receptor-mediated responses in the TN-GnRH neurons of adult teleost fish, the dwarf gourami, by means of gramicidin-perforated patch-clamp and cell-attached patch-clamp recordings. The reversal potential for the currents through GABA(A) receptors under the voltage clamp was depolarized relative to the resting membrane potential. GABA(A) receptor activation depolarized TN-GnRH neurons under the current clamp and had excitatory effect on their electrical activity, whereas the stronger GABA(A) receptor activation had bidirectional effect (excitatory-inhibitory). This excitatory effect is suggested to arise from high [Cl(-)](i) and was shown to be suppressed by bumetanide, the blocker of Cl(-)-accumulating sodium-potassium-2-chloride co-transporter (NKCC). The present results demonstrate that GABA(A) receptor activation induces excitation in TN-GnRH neurons, which may facilitate their neuromodulatory functions by increasing their spontaneous firing frequencies. The excitatory actions of GABA in the adult brain have recently been attracting much attention, and the easily accessible large TN-GnRH neurons should be a nice model system to analyze their physiological functions.
Nakane
Ryo
R
Dept. of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
Oka
Yoshitaka
Y
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D004594:Electrophysiology; D018846:Excitatory Amino Acids / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D006096:Gramicidin; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009830:Olfactory Bulb / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010473:Perciformes / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002712:Chlorides; D004232:Diuretics; D018846:Excitatory Amino Acids; D015221:Potassium Channels; D011963:Receptors, GABA-A; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D006096:Gramicidin; D007987:Gonadotropin-Releasing Hormone; D005680:gamma-Aminobutyric Acid