PRESYNAPTIC MECHANISMS IN THE SUPRACHIASMATIC NUCLEUS

点击翻译按钮获取中文摘要

DESCRIPTION (applicant's abstract): To maintain proper temporal coupling with the environment, neural systems have evolved that monitor changing conditions and communicate the information to the circadian clock. This biological clock senses day-night transitions via the retinohypothalamic tract (RHT), a direct glutamatergic projection from retinal ganglion cells to the suprachiasmatic nucleus (SCN). Activation of other afferent neural pathways can modify the light input signal. Presynaptic 5-HT1B, GABA-B, and neuropeptide Y receptors inhibit glutamate release from presynaptic RHT terminals and block light-induced phase shifts of circadian rhythms. The mechanisms of GABA-B, 5-HT1B, and neuropeptide Y receptor inhibition of glutamate release are not known. The inhibition of glutamate release by orphanin-FQ receptors at presynaptic RHT terminals will also be studied. How these multiple afferent inputs interact to regulate RHT activity has not been studied either in vivo or in vitro. Therefore, we have designed experiments using electrophysiological techniques to describe the cellular mechanisms presynaptic pathways use to modulate RHT activity and the environmental light signal. Slices of the hypothalamus containing the SCN with the optic nerve attached will be used to investigate the characteristics of glutamate release by recording evoked and spontaneous excitatory postsynaptic currents. The specific aims of the proposal are: 1) Identify the calcium channel subtypes that regulate the release of glutamate from presynaptic RHT terminals. 2) Determine the mechanisms coupling activation of GABA-B, 5-HT, and neuropeptide Y receptors with the inhibition of glutamate release from presynaptic RHT terminals. 3) Examine whether orphanin FQ receptors produce presynaptic inhibition of RHT terminals. 4) Investigate whether there are co-operative interactions between presynaptic neurotransmitter receptors regulating glutamate release from RHT terminals.