Abstract

This project will investigate how neurochemical signals interact within the SCN to synchronize circadian rhythms in behavior with the day-night cycle. Since disorders of the circadian timing system have been linked to a variety of mental illnesses, understanding the neurobiology of circadian rhythms should lead to the development of new treatments for these diseases. At least three different afferent projections of the SCN are involved in the photic entrainment of circadian rhythms. The RHT is a direct projection from the retina that is necessary and sufficient for entrainment. Projections from the raphe and the intergeniculate leaflet to the SCN also influence entrainment although they do not provide input necessary for the entrainment process. The neurochemical signals contained in these afferent projections as well as in neurons intrinsic to the SCN interact in a complex manner to control photic entrainment. The long-term goal of this project is to define the neurochemical basis of the entrainment of circadian rhythms by defining how photic information is communicated to and processed within the SCN.
Specific Aim I will test the hypothesis that an EAA is a neurotransmitter which communicates photic information to the SCN through the RHT. Since the investigator has been able to demonstrate that injection of an EAA agonist (i.e., NMDA) into the SCN in vivo can mimic the phase shifting effects of light, it will be possible to resolve a significant discrepancy about this hypothesis.
Specific Aim 2 will test the hypothesis that substance P, which appears to be contained in the RHT, contributes to the entrainment by modulating the activity of EAAs in the SCN.
Specific Aim 3 will investigate how the phase shifting effects of light are influenced by intrinsic SCN circuits and by afferent projections of the SCN. Specifically, the investigator will test the hypothesis that GABA, serotonin and NPY inhibit the phase shifting effects of light by inhibiting the phase shifting effects of EAAs and/or substance P in the SCN.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH058789-03
Application #
6186117
Study Section
Clinical Neuroscience and Biological Psychopathology Review Committee (CNBP)
Project Start
1998-08-01
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
3
Fiscal Year
2000
Total Cost
$192,483
Indirect Cost

  Institution

Name
Georgia State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
837322494
City
Atlanta
State
GA
Country
United States
Zip Code
30302

  Publications

Albers, H Elliott; Walton, James C; Gamble, Karen L et al. (2017) The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleus. Front Neuroendocrinol 44:35-82
Wang, L M; Schroeder, A; Loh, D et al. (2008) Role for the NR2B subunit of the N-methyl-D-aspartate receptor in mediating light input to the circadian system. Eur J Neurosci 27:1771-9
Novak, Colleen M; Ehlen, J Christopher; Paul, Ketema N et al. (2006) Light and GABA)(A) receptor activation alter period mRNA levels in the SCN of diurnal Nile grass rats. Eur J Neurosci 24:2843-52
Gamble, Karen L; Paul, Ketema N; Karom, Mary C et al. (2006) Paradoxical effects of NPY in the suprachiasmatic nucleus. Eur J Neurosci 23:2488-94
Ehlen, J Christopher; Novak, Colleen M; Karom, Mary C et al. (2006) GABAA receptor activation suppresses Period 1 mRNA and Period 2 mRNA in the suprachiasmatic nucleus during the mid-subjective day. Eur J Neurosci 23:3328-36
Ehlen, J Christopher; Albers, H Elliott; Breyer, Emelita D (2005) MEKC-LIF of gamma-amino butyric acid in microdialysate: systematic optimization of the separation conditions by factorial analysis. J Neurosci Methods 147:36-47
Paul, Ketema N; Fukuhara, Chiaki; Karom, Mary et al. (2005) AMPA/kainate receptor antagonist DNQX blocks the acute increase of Per2 mRNA levels in most but not all areas of the SCN. Brain Res Mol Brain Res 139:129-36
Gamble, Karen L; Ehlen, J Christopher; Albers, H Elliott (2005) Circadian control during the day and night: Role of neuropeptide Y Y5 receptors in the suprachiasmatic nucleus. Brain Res Bull 65:513-9
Gamble, K L; Novak, C M; Albers, H E (2004) Neuropeptide Y and N-methyl-D-aspartic acid interact within the suprachiasmatic nuclei to alter circadian phase. Neuroscience 126:559-65
Novak, C M; Albers, H E (2004) Novel phase-shifting effects of GABAA receptor activation in the suprachiasmatic nucleus of a diurnal rodent. Am J Physiol Regul Integr Comp Physiol 286:R820-5

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