Regulation of retinal input to the SCN

 To maintain proper temporal coupling between the circadian clock and the environment, neural systems have evolved that sense changing conditions and communicate the information to the clock. The daily change in light intensity (day/night) is the most important of these signals (zeitgebers). The biological clock receives light intensity information via the retinohypothalamic tract (RHT), a direct glutamatergic projection from retinal ganglion cells to SCN neurons. The RHT is both necessary and sufficient for entrainment of the SCN oscillator to the light-dark cycle. Activation of other afferent neural pathways can modify this light input signal and the behavioral responses to light. Presynaptic modulation of neurotransmitter release may involve inhibiting voltage-gated Ca2+ channels, inhibiting vesicular exocytosis, or activation of K+ channels. However, direct experimental evidence demonstrating the mechanisms of presynaptic inhibition of glutamate release from RHT terminals is lacking and the subject of current work. We are using electrophysiological techniques to describe the cellular mechanisms presynaptic pathways use to modulate RHT activity and the environmental light signal. Specific lines of research include 1) identifying the Ca2+ channel subtypes that regulate the release of glutamate from presynaptic RHT terminals, 2) determining the mechanisms coupling activation of GABAB, S-HT, and neuropeptide Y receptors with the inhibition of glutamate release from presynaptic RHT terminals. Experiments are being performed to determine whether GABAB, S-HT and neuropeptide receptors regulate presynaptic RHT terminals by inhibition of voltage-gated Ca2+ channels or activation of K+ channels, 3) examining whether orphanin-FQ receptors produce presynaptic inhibition of RHT terminals, and 4) investigating whether there are co-operative interactions between presynaptic neurotransmitter receptors mediating glutamate release from RHT terminals.