The Section on Functional Neuroanatomy combines molecular and neuroanatomical methods to identify dynamic aspects of nervous system function that relate to issues of mental health, infectious disease, and drug abuse. Drug and neurotransmitter receptors are mapped using in vitro ligand binding and autoradiography. In situ hybridization histochemistry is used to localize and quantify mRNA expression of neuropeptides, monoamine transporters and synthesizing enzymes, receptors, cytokines, and immediate-early genes in studies of adaptive changes to behavioral, pharmacological, or surgical interventions. 1) The cannabinoid receptor has been localized and quantified in Huntington's and Alzheimer's brains. 2) Studies of animal models of chronic stress are designed to elucidate brain mechanisms involved in the therapeutic amelioration of stress disorders. Antidepressant drug administration and electroconvulsive shock are used in the animal models. Brain systems responsive to both stress and therapeutic treatment include the corticotropin-releasing hormone (CRH) component of the hypothalamic paraventricular nucleus (PVN), which controls the hypothalamic-pituitary- adrenal axis, and the noradrenergic locus coeruleus, which plays a role in arousal and vigilance. 3) Expression of the mRNA for the immediate- early gene c-fos was used to map brain sites responsive to injections of interleukin-1. Responsive cells in the brainstem suggest a pathway by which peripheral cytokines, as mediators of immune or inflammatory challenges, affect neuroendocrine responses. 4) Combinations of anatomical markers are used to reveal activity changes in hypothalamic arcuate nucleus neurons with known neuropeptide phenotype and identified projections to the PVN.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH001090-18
Application #
5203682
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
1995
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Lehmann, Michael L; Mustafa, Tomris; Eiden, Adrian M et al. (2013) PACAP-deficient mice show attenuated corticosterone secretion and fail to develop depressive behavior during chronic social defeat stress. Psychoneuroendocrinology 38:702-15
Patchev, Alexandre V; Fischer, Dieter; Wolf, Siegmund S et al. (2007) Insidious adrenocortical insufficiency underlies neuroendocrine dysregulation in TIF-2 deficient mice. FASEB J 21:231-8
Steiner, Alexandre A; Chakravarty, Sumana; Rudaya, Alla Y et al. (2006) Bacterial lipopolysaccharide fever is initiated via Toll-like receptor 4 on hematopoietic cells. Blood 107:4000-2
Herkenham, Miles (2005) Folliculo-stellate (FS) cells of the anterior pituitary mediate interactions between the endocrine and immune systems. Endocrinology 146:33-4
Bryceson, Y T; Foster, J A; Kuppusamy, S P et al. (2005) Expression of a killer cell receptor-like gene in plastic regions of the central nervous system. J Neuroimmunol 161:177-82
Chakravarty, Sumana; Herkenham, Miles (2005) Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines. J Neurosci 25:1788-96
Steiner, Alexandre A; Chakravarty, Sumana; Robbins, Jared R et al. (2005) Thermoregulatory responses of rats to conventional preparations of lipopolysaccharide are caused by lipopolysaccharide per se-- not by lipoprotein contaminants. Am J Physiol Regul Integr Comp Physiol 289:R348-R352
Kassed, Cheryl A; Herkenham, Miles (2004) NF-kappaB p50-deficient mice show reduced anxiety-like behaviors in tests of exploratory drive and anxiety. Behav Brain Res 154:577-84
Foster, Jane A; Puchowicz, Michael J; McIntyre, Dan C et al. (2004) Activin mRNA induced during amygdala kindling shows a spatiotemporal progression that tracks the spread of seizures. J Comp Neurol 476:91-102
Butterweck, Veronika; Winterhoff, Hilke; Herkenham, Miles (2003) Hyperforin-containing extracts of St John's wort fail to alter gene transcription in brain areas involved in HPA axis control in a long-term treatment regimen in rats. Neuropsychopharmacology 28:2160-8

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