Studies will continue to focus on the intrinsic organization of the mediobasal hypothalamus. We plan to use a combination of light and electron microscopy to study Golgi impregnated and immunocytochemically stained tissue from the rat medial hypothalamus, concentrating on those areas which play an important role in neuroendocrine regulation. Using several double ultrastructural immunostaining methods developed in our lab, particular attention will be paid to characterizing the transmitters, peptides, and pituitary tropins found in both pre-synaptic and post-synaptic neurons in this part of the brain. Combinations of pre-embedding immunostaining with peroxidase and silver-intensified colloidal gold and post-embedding immunostaining with colloidal gold will be used to localize and characterize neurons and axonal endings containing various neuroactive substances. The question of subcellular localization of several neuroactive substances will be addressed with a quantitative evaluation of post-embedding immunostaining with colloidal gold particles. Cells which send efferent axonal projections to the median eminence will be identified with retrograde transport of cholera toxin conjugated to horseradish peroxidase; the pituitary tropin contained in these cells will be identified with post-embedding immunocytochemistry using 5 nm colloidal gold adsorbed to Protein A or a secondary immunoglobulin as a marker, and the neurotransmitters of synaptic terminals on identified cells will be labeled with 10 nm colloidal gold. This should allow a precise characterization of the neuroactive substances which are in direct synaptic contact with neurons with identified pituitary tropins which project to the median eminence. Golgi silver chromate impregnations and horseradish peroxidase intracellular filling will be combined with ultrastructural and immunocytochemical analyses to study the dendritic trees of immunocytochemically identified neurons; afferent boutons which are in synaptic contact with peroxidase- or Golgi- labeled dendritic trees will be immunocytochemically identified, and the relative synaptic efficacy of identified boutons will be estimated on the basis of a computer-assisted correlation between light and electron microscopy of this material. The hypothesis that estrogen-induced pituitary prolactin cell tumors may result from insult to hypothalamic dopamine neurons will be examined immunocytochemically.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS016296-07A1
Application #
3396791
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1980-03-01
Project End
1990-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
7
Fiscal Year
1987
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
Obrietan, K; van den Pol, A N (1996) Neuropeptide Y depresses GABA-mediated calcium transients in developing suprachiasmatic nucleus neurons: a novel form of calcium long-term depression. J Neurosci 16:3521-33
van den Pol, A N; Strecker, G J; Dudek, F E (1996) Excitatory and inhibitory amino acids and synaptic transmission in the suprachiasmatic nucleus. Prog Brain Res 111:41-56
Romano, C; van den Pol, A N; O'Malley, K L (1996) Enhanced early developmental expression of the metabotropic glutamate receptor mGluR5 in rat brain: protein, mRNA splice variants, and regional distribution. J Comp Neurol 367:403-12
Romano, C; Sesma, M A; McDonald, C T et al. (1995) Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain. J Comp Neurol 355:455-69
van den Pol, A N; Romano, C; Ghosh, P (1995) Metabotropic glutamate receptor mGluR5 subcellular distribution and developmental expression in hypothalamus. J Comp Neurol 362:134-50
Obrietan, K; Van den Pol, A N (1995) Calcium hyperexcitability in neurons cultured with glutamate receptor blockade. J Neurophysiol 73:1524-36
Obrietan, K; Belousov, A B; Heller, H C et al. (1995) Adenosine pre- and postsynaptic modulation of glutamate-dependent calcium activity in hypothalamic neurons. J Neurophysiol 74:2150-62
van den Pol, A N (1995) Presynaptic metabotropic glutamate receptors in adult and developing neurons: autoexcitation in the olfactory bulb. J Comp Neurol 359:253-71
Chen, G; Trombley, P Q; van den Pol, A N (1995) GABA receptors precede glutamate receptors in hypothalamic development;differential regulation by astrocytes. J Neurophysiol 74:1473-84
van den Pol, A N; Hermans-Borgmeyer, I; Hofer, M et al. (1994) Ionotropic glutamate-receptor gene expression in hypothalamus: localization of AMPA, kainate, and NMDA receptor RNA with in situ hybridization. J Comp Neurol 343:428-44

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