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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034586-04
Application #
2669067
Study Section
Psychobiology, Behavior, and Neuroscience Review Committee (PBN)
Program Officer
Kitt, Cheryl A
Project Start
1995-04-01
Project End
2000-02-29
Budget Start
1998-03-01
Budget End
2000-02-29
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Georgia State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
837322494
City
Atlanta
State
GA
Country
United States
Zip Code
30302
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
Gillespie, C F; Van Der Beek, E M; Mintz, E M et al. (1999) GABAergic regulation of light-induced c-Fos immunoreactivity within the suprachiasmatic nucleus. J Comp Neurol 411:683-92
Huhman, K L; Jasnow, A M; Sisitsky, A K et al. (1999) Glutamic acid decarboxylase mRNA in the suprachiasmatic nucleus of rats housed in constant darkness. Brain Res 851:266-9
Mintz, E M; Marvel, C L; Gillespie, C F et al. (1999) Activation of NMDA receptors in the suprachiasmatic nucleus produces light-like phase shifts of the circadian clock in vivo. J Neurosci 19:5124-30
Mintz, E M; Albers, H E (1997) Microinjection of NMDA into the SCN region mimics the phase shifting effect of light in hamsters. Brain Res 758:245-9
Huhman, K L; Marvel, C L; Gillespie, C F et al. (1997) Tetrodotoxin blocks NPY-induced but not muscimol-induced phase advances of wheel-running activity in Syrian hamsters. Brain Res 772:176-80
Gillespie, C F; Mintz, E M; Marvel, C L et al. (1997) GABA(A) and GABA(B) agonists and antagonists alter the phase-shifting effects of light when microinjected into the suprachiasmatic region. Brain Res 759:181-9
Huhman, K L; Gillespie, C F; Marvel, C L et al. (1997) Peptidergic mechanisms of action in the suprachiasmatic nucleus. Ann N Y Acad Sci 814:300-4
Gillespie, C F; Huhman, K L; Babagbemi, T O et al. (1996) Bicuculline increases and muscimol reduces the phase-delaying effects of light and VIP/PHI/GRP in the suprachiasmatic region. J Biol Rhythms 11:137-44
Huhman, K L; Hennessey, A C; Albers, H E (1996) Rhythms of glutamic acid decarboxylase mRNA in the suprachiasmatic nucleus. J Biol Rhythms 11:311-6

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