This project will investigate how several neurotransmitter systems interact to control circadian rhythms in behavior. Understanding the basic principles underlying the neurobiology of circadian rhythms should lead to the development of new treatments for a variety of mental illnesses. The unifying theme of this proposal is that GABAergic neurons within the suprachiasmatic nucleus of the hypothalamus (SCN) play a critical role in regulating the phase shifting of circadian rhythms. We will test the general hypothesis that GABA alters the phase shifting capacity of the three major afferents to the SCN (i,e. the retinohypothalamic tract, the geniculohypothalamic tract ant eh projection from the raphe) as well as the phase shifting capacity a group of neurons intrinsic to the SCN. Specifically, we will investigate how GABA interacts with the primary neurotransmitters in the afferent projections (i.e. glutamate, neuropeptide Y (NPY) and serotonin) as well as with the major neurotransmitters within the ventrolateral SCN (i.e. vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI) and gastrin releasing peptide (GRP)).
Specific aim 1 will test the hypothesis that GABAergic activity within the SCN mediates the phase shifting effects of both NPY and serotonin during the middle of the subjective day (i.e. circadian time 6).
Specific aim 2 will test the hypothesis that GABAergic drugs block the phase delaying effects of light at the beginning of the subjective night (i.e. circadian time 12-14) by their effects on glutamate or serotonin activity within the SCN.
Specific aim 3 will test the hypothesis that GABAergic drugs modulate the phase delaying effects of VIP, PHI and GRP that occur at circadian time 12-14.
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