Section on Functional Neuroanatomy (SFN)
Laboratory of Cellular and Molecular Regulation
Dr. Herkenham received a B.A. in Psychology from Amherst College in 1970 and a Ph.D. in Physiological Psychology from Northeastern University in 1975. He did postdoctoral training with Dr. W.J.H. Nauta at M.I.T. where he began a long career in neuroanatomical localization studies. Dr. Herkenham joined the NIMH IRP in 1977. In addition to being a Section Chief, he is the Acting Chief of the Laboratory of Cellular and Molecular Regulation (LCMR). He has published in the areas of neuronal tract tracing, opioid and cannabinoid receptor localization, therapeutic actions of antidepressant drugs, the neural circuitry underlying the deleterious effects of chronic psychosocial stress, the beneficial effects of environmental enrichment on mood states, immune signal molecule induction and function in the developing and adult brain, and antidepressant effects of lymphocytes adoptively transferred into naïve mice from chronically stressed mice.
Our group uses modern neuroanatomical and molecular tools to investigate nervous system regulatory events that occur in animals when they respond and adapt to immune challenges, drug administration, psychosocial stress, or environmental enrichment. Behavior is characterized in validated tests for anxiety, depression, and social interactions. Responsive brain structures and cell types are identified and characterized by GFP-positive cell tracking in reporter animals, immunohistochemistry, in situ hybridization histochemistry, and cell sorting followed by phenotypic analyses. In addition to histochemical tools, we perform quantitative molecular assays for gene expression and protein levels as well as in vitro and ex vivo assays of isolated neurons, glia, and lymphocytes. We have examined the relationships among defeat-induced depressive states and environmental enrichment, the basis for stress resiliency or susceptibility, responsive brain circuits, and roles played by adult neurogenesis and adrenal hormones. Recent work on bi-direcitonal communication between the brain and the immune system showed the effects of immune cells as anti-depressant agents. Our studies guide further cellular work aimed at understanding the circuit, cellular, and molecular bases for altered emotionality.
Lymphocytes from chronically stressed mice confer antidepressant-like effects to naïve mice. . 1. Brachman, R.A., Lehmann, M.L., Maric, D., and Herkenham, M.. J. Neurosci. 35: 1530-1538, 2015 PMID: 25632130.
Minimal NF-kB activity in neurons. . Listwak, S.J., Rathore, P., and Herkenham, M.. Neuroscience. 2013, 250: 282-299, 2013. PMID: 0.
Glucocorticoids orchestrate divergent effects on mood through adult neurogenesis. . 3. Lehmann, M.L., Brachman, R.A., Martinowich, K., Schloesser, R.J., and Herkenham, M.. J. Neurosci.. 2013, 33: 2961-2972. PMID: 0.
Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response. . 4. Oskvig, D. B., Elkahloun, A. G., Johnson, K. R., Phillips, T. M. and Herkenham, M.. Brain, Behavior, Immun.. 26: 623-634, 2012. PMID: 0.
Environmental enrichment confers stress resiliency to social defeat through an infralimbic cortex-dependent neuroanatomical pathway . Lehmann, M.L. and Herkenham, M.. J. Neuroscience. 31: 6159-6173, 2011. PMID: 0.
Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress. . 6. Schloesser, R.J., Lehmann, M., Martinowich, K., Manji, H.K., Herkenham, M.. Mol. Psychiatry. 2010, 15: 1152-1163. PMID: 0.
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