Our goal is to determine the anatomical and neurochemical bases of neuronal control of gonadotrophin secretion. The """"""""premium movens"""""""" of gonadotrophin secretion is the gonadotrophin hormone releasing hormone (GNRH) produced by a discrete group of hypothalamic neurons. The feed- back effects of estrogens of GNRH release are mediated in part by estrogen sensitive neuronal circuits which control the activity of the GNRH producing neurons. The control of GNRH delivery systems is differently organized in rodent and primates, at least in part because of anatomical differences such as the intranuclear location of both the GNRH producing - and their related estrogen sensitive neurons in primates, as opposed to the internuclear GNRH delivery system in rats where the GNRH neurons are located in the medial preoptic area. The proposed experiments will contribute to the following aims: a) to complete the identification of the primary circuits of estrogen sensitive neurons supporting the GNRH neurons in the rat, b) to pursue the origins of these circuits in the hypothalamus and extrahypothalamic areas, c) to determine the degree of similarity between the internuclear system of GNRH control in the rat and the intranuclear control in the monkey. Electron microscopic double immunostaining combined with degeneration, antero- and retrograde tracer techniques will be employed to answer the following specific questions: 1) What is the anatomical basis of the interactions between the mediobasal hypothalamus GABA-,dopamine-, and opiocortin systems in the rat? 2) What is the interrelationship between GABAergic-, catecholaminergic-, and GNRH-neurons in the rat medial preoptic area? 3) How do mediobasal hypothalamus opioid peptide- containing neurons regulate norepinephrine/epinephrine cells projecting to the mediobasal hypothalamus and medial preoptic ara? 4) Is the catecholaminergic innervation of GNRH neurons in the rhesus monkey analogous to that in the rat? Do monkey GNRH neurons receive direct information from GABAergic progesterone receptor-containing hypothalamic neurons?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD023830-03
Application #
3324149
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1989-09-01
Project End
1993-04-30
Budget Start
1991-09-01
Budget End
1993-04-30
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Leranth, C; Shanabrough, M (2001) Supramammillary area mediates subcortical estrogenic action on hippocampal synaptic plasticity. Exp Neurol 167:445-50
Leranth, C; Shanabrough, M; Horvath, T L (2000) Hormonal regulation of hippocampal spine synapse density involves subcortical mediation. Neuroscience 101:349-56
Leranth, C; Roth, R H; Elsworth, J D et al. (2000) Estrogen is essential for maintaining nigrostriatal dopamine neurons in primates: implications for Parkinson's disease and memory. J Neurosci 20:8604-9
Leranth, C; Shanabrough, M; Horvath, T L (1999) Estrogen receptor-alpha in the raphe serotonergic and supramammillary area calretinin-containing neurons of the female rat. Exp Brain Res 128:417-20
Holderith, N; Varoqueaux, F; Borhegyi, Z et al. (1998) Dual (excitatory and inhibitory) calretinin innervation of AMPA receptor-containing neurons in the rat lateral septum. Exp Brain Res 119:65-72
Horvath, T L; Bechmann, I; Naftolin, F et al. (1997) Heterogeneity in the neuropeptide Y-containing neurons of the rat arcuate nucleus: GABAergic and non-GABAergic subpopulations. Brain Res 756:283-6
Naftolin, F; Horvath, T L; Jakab, R L et al. (1996) Aromatase immunoreactivity in axon terminals of the vertebrate brain. An immunocytochemical study on quail, rat, monkey and human tissues. Neuroendocrinology 63:149-55
Horvath, T L; Naftolin, F; Leranth, C et al. (1996) Morphological and pharmacological evidence for neuropeptide Y-galanin interaction in the rat hypothalamus. Endocrinology 137:3069-78
Leranth, C; Kiss, J (1996) A population of supramammillary area calretinin neurons terminating on medial septal area cholinergic and lateral septal area calbindin-containing cells are aspartate/glutamatergic. J Neurosci 16:7699-710
Hof, P R; Glezer, I I; Revishchin, A V et al. (1995) Distribution of dopaminergic fibers and neurons in visual and auditory cortices of the harbor porpoise and pilot whale. Brain Res Bull 36:275-84

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