Title: Excitatory Action of Gaba in the Terminal Nerve Gonadotropin-releasing Hormone

20 The terminal nerve (TN)-gonadotropin-releasing hormone (GnRH) neurons have been 21 suggested to function as a neuromodulatory system that regulates the motivational and 22 arousal state of the animal and have served as a model system for the study of GnRH 23 neuron physiology. To investigate the synaptic control of the TN-GnRH neurons, we 24 analyzed electrophysiologically the effect of GABA on the TN-GnRH neurons. GABA 25 generally hyperpolarizes most of the neurons in the adult brain by activating GABAA 26 receptors while the activation of GABAA receptors depolarizes some specific neurons in 27 the mature brain. Here, we examined the GABAA receptor-mediated responses in the 28 TN-GnRH neurons of adult teleost fish, the dwarf gourami, by means of gramicidin 29 perforated patch-clamp and cell-attached patch-clamp recordings. The reversal potential 30 for the currents through GABAA receptors under the voltage clamp was depolarized 31 relative to the resting membrane potential. GABAA receptor activation depolarized 32 TN-GnRH neurons under the current clamp and had excitatory effect on their electrical 33 activity, while the stronger GABAA receptor activation had bidirectional effect 34 (excitatory inhibitory). This excitatory effect is suggested to arise from high [Cl]i 35 and was shown to be suppressed by bumetanide, the blocker of Cl-accumulating 36 sodium-potassium-2-chloride co-transporter (NKCC). The present results demonstrate 37 that GABAA receptor activation induces excitation in TN-GnRH neurons, which may 38 facilitate their neuromodulatory functions by increasing their spontaneous firing 39 frequencies. The excitatory actions of GABA in the adult brain have recently been 40 attracting much attention, and the easily accessible large TN-GnRH neurons should be a 41 nice model system to analyze their physiological functions. 42 43