Circadian rhythms are internally generated rhythms in behavior and physiology with periods of about 24 hours. Awareness of underlying circadian rhythmicity is essential for all pharmacological treatments. Circadian rhythms can be used to advantage in medical treatments, for example, by timing drug delivery to minimize toxic side effects. Internal rhythms must be reset to maintain synchrony with the external cycle of 24 hours. Better understanding of the resetting mechanisms will allow advances in the treatment of discomforts associated with jet lag and shift work, as well as a variety of depressive disorders.

Mary E. Harrington Neural Control of Circadian Rhythms Several types of stimuli are able to phase shift the circadian clock. Light produces phase shifts mainly during the subjective night, with a characteristic phase response curve (PRC), the "LPRC." Other stimuli, including dark pulses, activity within a novel running wheel, and benzodiazepine injections, produce phase shifts mainly during the subjective day, in the "DPRC" pattern. By measuring wheel-running rhythms of hamsters, we can study the neural, pharmacological, and behavioral substrates of these different patterns of phase shifts.

The mammalian circadian pacemaker is localized to the hypothalamic suprachiasmatic nuclei (SCN). We are using the brain slice preparation to measure circadian oscillations from the SCN maintained in vitro. Currently we measure these oscillations by sampling spontaneous neural activity using extracellular electrophysiological recordings. We can use this preparation to study circadian clock phase shifts induced by various neurotransmitters. One of my current interests is in the cellular events that accompany phase shifts of the circadian clock in either the LPRC or DPRC pattern. I am also interested in understanding the mechanisms by which the suprachiasmatic nucleus imposes a circadian rhythm on behavior. This work may lead to a better understanding of resetting and rhythm-generating mechanisms underlying mammalian circadian rhythmicity.   For additional information, please visit Smith College Home Page Harrington Lab at Smith College

M.E. Harrington and K.M. Schak*, Neuropeptide Y phase advances the in vitro hamster circadian clock during the subjective day with no effect on phase during the subjective night, Canadian Journal of Pharmacology and Physiology, 78 (2000) 87-92.

P.C. Yannielli and M.E. Harrington, Neuropeptide Y applied in vitro can block the phase shifts induced by light in vivo, NeuroReport, 11 (2000) 1587-1591.

M.E. Harrington, S.M. Biello and P. Panula, Effects of histamine on circadian rhythms and hibernation, Biological Rhythms Research, 31 (2000) 374-390.

PC Yannielli and ME Harrington, Neuropeptide Y in the mammalian system: Effects on light-induced circadian responses, Peptides, 22 (2001) 547-556.

K.M. Schak*, S.P. Scordilis, G. Ferreyra, M.E. Harrington, Neuropeptide Y activates protein kinase C in hamster suprachiasmatic nuclei brain slices, Biological Rhythm Research,32 (2001) 201-206.

P.C. Yannielli and M.E. Harrington, The neuropeptide Y5 receptor mediates the blockade of "photic-like" NMDA-induced phase shifts, Journal of Neuroscience, 21 (2001) 5367-5373.

C. Fukuhara, J. McKinley Brewer, J.C. Dirdena, E.L. Bittman, G. Tosini and M.E. Harrington, Neuropeptide Y rapidly reduces period1 and period2 mRNA levels in the hamster suprachiasmatic nucleus, Neuroscience Letters, 314 (2001) 119-122.

J. McKinley Brewer, P.C. Yannielli and M.E. Harrington, Neuropeptide Y differentially suppresses per1 and per2 mRNA induced by light in the suprachiasmatic nuclei of the golden hamster, Journal of Biological Rhythms,17 (2002) 28-39.

P.C. Yannielli, J. McKinley Brewer and M.E. Harrington, Is novel wheel inhibition of per1 and per2 expression linked to phase shift occurrence?, Neuroscience, 112 (2002) 677-685.

C.A. Christian* and M.E. Harrington, Three days of novel wheel access diminishes light-induced phase delays in vivo with no effect on per1 induction by light, Chronobiology International, 19 (2002) 671-682.

A.C. Hall and M.E. Harrington, 'Experimental Methods in Neuroscience': an undergraduate neuroscience laboratory course for teaching ethical issues, laboratory techniques, experimental design and analysis, The Journal of Undergraduate Neuroscience Education, 2 (2003) A1-A7.

PC Yannielli, J. McKinley Brewer and M.E. Harrington, Activation of the NPY Y5 receptor suppresses circadian responses to light while its blockade potentiates them: complementary in vivo and in vitro studies. European Journal of Neuroscience, 18 (2004) 891-897.

Hai-Ying M. Cheng, Karl Obrietan, Sean W. Cain, Bo Young Lee, Patricia V. Agostino, Nicholas A. Joza, Mary E. Harrington, Martin R. Ralph, Josef M. Penninger (2004) Dexras1 potentiates photic and suppresses non-photic responses of the circadian clock, Neuron, 43: 715-728.

PC Yannielli and ME Harrington (2004) Let there be 'more' light: enhancement of light actions on the circadian system through non-photic pathways, Progress in Neurobiology 74: 59-76.

S Soscia* and ME Harrington, Neuropeptide Y attenuates NMDA-induced phase shifts in the SCN of the NPY Y1 receptor knockout mice in vitro, Brain Research, 1023 (2004) 148-153.

S. Soscia* and ME Harrington (in press) Neuropeptide Y does not reset the circadian clock in NPY Y2-/- mice, Neuroscience Letters

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