The suprachiasmatic nucleus of the hypothalamus (SCN) is the location of the primary circadian clock in mammals. This clock drives daily rhythms and behavior using both humoral and neural outputs. The clock receives numerous inputs from other brain regions, but the most prominent of these are glutamatergic projections from the retina, serotonergic projections from the midbrain raphe, and neuropeptide Y (NPY) containing projections from the intergeniculate leaflets of the thalamus. Photic information from the retina helps to synchronize the timing of the circadian clock with the environment, but these signals can be modulated by changes in the amount of serotonin or NPY being released in the SCN. This proposal focuses on using reverse microdialysis perfusion of drugs into the SCN region of the Syrian hamster to test specific hypotheses about the function of serotonin and NPY in the hamster circadian system. These hypotheses are: 1) Do serotonin and NPY inhibit both the phase delaying and phase advancing effects of light? 2) Does the sensitivity of the SCN to serotonin and NPY vary with circadian time, and 3) Are variations in sensitivity of the SCN to exogenous stimulation by serotonin and NPY driven by variation in endogenous stimulation levels? These hypotheses will be tested by infusing specific serotonin and NPY agonists and antagonists into the SCN region, and measuring how these injections alter the phase shifting effects of light. Finally, we will begin to examine the hypothesis that the effects of serotonin and NPY on circadian rhythmicity are mediated by GABA. The experiments of this proposal will lead to a greater understanding of how the serotonin and NPY neurotransmitter systems modulate circadian rhythms, and lead to future investigations of the functional relevance of these neurotransmitters in the normal function of the circadian system.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Academic Research Enhancement Awards (AREA) (R15)
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Special Emphasis Panel (ZRG1-IFCN-3 (01))
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Mitler, Merrill
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Kent State University at Kent
Schools of Arts and Sciences
United States
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Kallingal, George J; Mintz, Eric M (2014) Site-specific effects of gastrin-releasing peptide in the suprachiasmatic nucleus. Eur J Neurosci 39:630-9
Kallingal, George J; Mintz, Eric M (2007) Gastrin releasing peptide and neuropeptide Y exert opposing actions on circadian phase. Neurosci Lett 422:59-63
Mintz, Eric M; Scott, Tamara J (2006) Colocalization of serotonin and vesicular glutamate transporter 3-like immunoreactivity in the midbrain raphe of Syrian hamsters (Mesocricetus auratus). Neurosci Lett 394:97-100
Haak, Laurel L; Albers, H Elliott; Mintz, Eric M (2006) Modulation of photic response by the metabotropic glutamate receptor agonist t-ACPD. Brain Res Bull 71:97-100
Kallingal, George J; Mintz, Eric M (2006) Glutamatergic activity modulates the phase-shifting effects of gastrin-releasing peptide and light. Eur J Neurosci 24:2853-8