The goal of this research is to determine how forebrain systems and neuropeptide-defined pathways control the neuroendocrine, autonomic and visceral neural systems in mammals. The short range goals of the research focus on three related issues: (1) How are circadian rhythms regulated in the central nervous systems? The effect of lighting schedule, feeding and drinking schedules, as well as physiological and pharmacological manipulations on the functions of central pacemakers in the albino rat will be studied. Longitudinal assays of overt motor activity, ingestive behaviors and neurophysiological activity will complement cross sectional analyses of opioid peptide levels, opiate receptor binding, metabolism, (by the 2-deoxyglucose method) and ultrastructural changes in hypothalamic regions thought to contain the primary (suprachiasmatic nucleus) and secondary (lateral hypothalamic area, e.g.) circadian pacemakers. The way the body responds to environmental and internal stress, disease states and drug therapy depends heavily on the functions of the circadian rhythm systems, therefore, understanding how these rhythms operate will increase our ability to maximize our own adaptation and survival. (2) In a related series of experiments, opioid peptide systems, especially the dynorphin-containing systems, are investigated for their role in the control of the neuroendocrine, autonomic and visceral neural systems. Preliminary studies suggest that the opioid neural systems are strategically placed to regulate not only circadian rhythms, but also other phylogenetically ancient motor systems related to eating, drinking, digestion, cardiovascular and respiratory control. The studies will aid in our understanding of how peptide systems control these important regulatory functions. The combined immunofluorescence and retrograde fluorescence tracing method will be used to determine connections of dynorphin-(and some enkephalin-) containing neurons in structures that innervate and control and peripheral sympathetic, parasympathetic, and neuroendocrine neural systems. (3) In the third group of experiments, """"""""higher centers"""""""" that may regulate circadian rhythm generators and other motor neural systems will be investigated with new neuroanatomical methodologies. In particular, the efferents of the ventral pallidium to the hypothalamus, hypothalamus to brainstem, and convergence of retinal, ventral lateral geniculate nucleus, dorsal raphe and ventral pallidal inputs to hypothalamus will be studied with anterograde and retrograde techniques which overcome the problem of uptake of tracer by fibers of passage. These studies are important in that they will help elucidate the morphological substrates by which """"""""higher"""""""" and """"""""lower"""""""" brain centers integrate the classical motor systems, circadian rhythms, neuroendocrine systems, pituitary, and autonomic and visceral motor systems of the body.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS015321-08
Application #
3396142
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1979-12-01
Project End
1989-01-31
Budget Start
1987-02-01
Budget End
1988-01-31
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Fallon, J; Reid, S; Kinyamu, R et al. (2000) In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain. Proc Natl Acad Sci U S A 97:14686-91
Solbrig, M V; Koob, G F; Fallon, J H et al. (1996) Prefrontal cortex dysfunction in Borna disease virus (BDV)--infected rats. Biol Psychiatry 40:629-36
Solbrig, M V; Koob, G F; Fallon, J H et al. (1994) Tardive dyskinetic syndrome in rats infected with Borna disease virus. Neurobiol Dis 1:111-9
Back, S A; Colon, M; Fallon, J H et al. (1993) Ventral mesencephalic and cortical transplants into the rat striatum display enhanced activity for neutral endopeptidase 24.11 ('enkephalinase';CALLA). Brain Res 612:85-95
Giolli, R A; Torigoe, Y; Clarke, R J et al. (1992) GABAergic and non-GABAergic projections of accessory optic nuclei, including the visual tegmental relay zone, to the nucleus of the optic tract and dorsal terminal accessory optic nucleus in rat. J Comp Neurol 319:349-58
Fallon, J H; Di Salvo, J; Loughlin, S E et al. (1992) Localization of acidic fibroblast growth factor within the mouse brain using biochemical and immunocytochemical techniques. Growth Factors 6:139-57
Ciofi, P; Fallon, J H; Croix, D et al. (1991) Expression of neuropeptide Y precursor-immunoreactivity in the hypothalamic dopaminergic tubero-infundibular system during lactation in rodents. Endocrinology 128:823-34
Christmas, P; Callaway, J; Fallon, J et al. (1991) Selective secretion of annexin 1, a protein without a signal sequence, by the human prostate gland. J Biol Chem 266:2499-507
Giolli, R A; Blanks, R H; Torigoe, Y et al. (1990) Opioid receptors in the accessory optic system of the rat: effects of monocular enucleation. Vis Neurosci 5:497-506
Fallon, J H; Annis, C M; Gentry, L E et al. (1990) Localization of cells containing transforming growth factor-alpha precursor immunoreactivity in the basal ganglia of the adult rat brain. Growth Factors 2:241-50

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