Circadian rhythmicity of mammals is regulated primarily by photoperiod interacting with a clock in the brain. This clock, the suprachiasmatic nucleus (SCN), times the expression of physiological and behavior events that repeat approximately every 24 hr. Light information reaches the SCN directly via a retinohypothalamic tract and indirectly via a geniculohypothalamic tract. The latter is derived from NPY and other, presently unidentified, cell types in the intergeniculate leaflet (IGL). In addition, there is extensive innervation of the IGL and SCN by serotonergic cells of the midbrain raphe nuclei. Destruction of these cells substantially modifies the expression of hamster circadian rhythmicity. The present set of experiments will elucidate the neuroanatomy of this system and the extent to which it controls the circadian locomotor rhythm.
The specific aims i nclude: a) delineation of the raphe cells and their neuromodulator type projecting to SCN, IGL and superior colliculus; b) description of the circuitry involving the enkephalinergic cells of the IGL and VLG and their contribution to the geniculohypothalamic tract; c) determination of the extent to which the neurotransmitter, serotonin, regulates circadian rhythm phase, period or magnitude by acting through the IGL or SCN; d) direct confirmation that serotonin is the transmitter acting through specific receptors to regulate the circadian rhythm system. Immunohistological and immunohistofluorescent methods will identify cells and fibers. Receptor autoradiography will identify serotonergic receptor types in the SCN and IGL. The neurotoxins, N-methyl-d-aspartate and 5,7- dihydroxytryptamine, will be used to make lesions of elements of the neural system under investigation. An understanding of the basic neuroanatomy of the circadian rhythm system will facilitate development of behavioral and pharmacological therapies for the treatment of circadian rhythm-based sleep disorders and mental health pathologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS022168-07
Application #
3404249
Study Section
Biopsychology Study Section (BPO)
Project Start
1992-05-08
Project End
1995-03-31
Budget Start
1992-05-08
Budget End
1993-03-31
Support Year
7
Fiscal Year
1992
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Morin, Lawrence P (2013) Neuroanatomy of the extended circadian rhythm system. Exp Neurol 243:4-20
Morin, Lawrence P; Hefton, Sara; Studholme, Keith M (2011) Neurons identified by NeuN/Fox-3 immunoreactivity have a novel distribution in the hamster and mouse suprachiasmatic nucleus. Brain Res 1421:44-51
Morin, Lawrence P; Lituma, Pablo J; Studholme, Keith M (2010) Two components of nocturnal locomotor suppression by light. J Biol Rhythms 25:197-207
Morin, L P; Studholme, K M (2009) Millisecond light pulses make mice stop running, then display prolonged sleep-like behavior in the absence of light. J Biol Rhythms 24:497-508
Goz, Didem; Studholme, Keith; Lappi, Douglas A et al. (2008) Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms. PLoS One 3:e3153
Vidal, Luis; Morin, Lawrence P (2007) Absence of normal photic integration in the circadian visual system: response to millisecond light flashes. J Neurosci 27:3375-82
Morin, Lawrence P (2007) SCN organization reconsidered. J Biol Rhythms 22:3-13
Morin, L P; Allen, C N (2006) The circadian visual system, 2005. Brain Res Rev 51:1-60
Muscat, L; Morin, L P (2006) Intergeniculate leaflet: contributions to photic and non-photic responsiveness of the hamster circadian system. Neuroscience 140:305-20
Morin, L P; Shivers, K-Y; Blanchard, J H et al. (2006) Complex organization of mouse and rat suprachiasmatic nucleus. Neuroscience 137:1285-97

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