Studies of Central Nervous System Functional Anatomy

Herkenham, M.

Abstract

A sensitive method for light microscopic localization of brain receptors by in vitro autoradiography was developed previously in this laboratory. By this method we have mapped the locations of drug and neurotransmitter receptors in the brains of rats and other vertebrates, including primates. Radiolabeled ligand binding using subtype-selective assay conditions confirmed the existence of anatomically distinct mu, delta, and kappa opiate receptor subtypes. A similar strategy led to the visualization of separate tachykinin receptors marked by radiolabeled substance P and eledoisin. Immunohistochemistry is used to compare the distributions of putative neurotransmitters and their receptors. The relationship of these localization patterns with other markers of brain heterogeneity, provided by tract tracing and enzyme staining, allows hypotheses about functional circuitry in the central nervous system. Physiological activation of neurochemically defined systems may lead to receptor occupation or regulation, which can be revealed and localized by in vivo as well as in vitro autoradiographic techniques.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Mental Health (NIMH)
• Type: Intramural Research (Z01)
• Project #: 1Z01MH001090-10
• Application #: 3968484
• Support Year: 10
• Fiscal Year: 1986

Institution

• Name: U.S. National Institute of Mental Health
• Country: United States

Publications

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

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

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

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