GLUTAMATE NEURONS IN HYPOTHALAMUS REGULATE EXCITATORY TRANSMISSION

The hypothalamus is the crucial part of the brain that regulates homeo stasis throughout the body. It governs the endocrine and autonomic ner vous systems, temperature, heart rate, emotional and motivational stat es, reproduction, energy and water balances, and circadian rhythms. In contrast to the prevailing belief that hypothalamic neurons use pepti des, neuromodulators, or other slow-acting agents as their principal n euroactive substances, we present data indicating that the primary exc itatory transmitter released by medial hypothalamic neurons is glutama te. This surprising new evidence is based on three converging approach es: Immunogold cytochemistry revealed that some hypothalamic neurons a nd their processes in vitro contained high amounts of immunoreactive g lutamate. Ca2+ digital video imaging showed that cytoplasmic Ca2+ leve ls of cultured neurons, elevated because of spontaneous presynaptic re lease of a hypothalamic transmitter, were reduced by perfusion with th e selective glutamate receptor antagonists cyano-2,3-di-hydroxy-7-nitr oquinoxaline and 2-aminophosphonovaleric acid. Electrophysiological an alysis of whole-cell patch-clamp recordings from single and pairs of m onosynaptically coupled hypothalamic neurons in culture showed that vi rtually all spontaneous and evoked EPSPs appear to be mediated by syna ptic secretion of glutamate.