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NINDSNIMHNICHDNIDCDNEINIDCRNIANIAAANIDANHGRI NCCIHNIDDKNIEHSCCB

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Senior Investigator

Miles Herkenham, Ph.D.

Porter Neuroscience Research Center
Building 35 Room 1C-913
35 Convent Drive MSC 3724
Bethesda MD 20892-3724
Office: (301) 496-8288


herkenh@mail.nih.gov

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 flow cytometry. We perform quantitative molecular assays for gene expression and protein levels as well as in vitro and ex vivo assays of isolated neurons, glia, neural stem cells, 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-directional 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.

Additional information can be found at the lab website, at http://intramural.nimh.nih.gov/lcmr/sfn/

Staff Image
  • Chelsie Crossen
    Post baccalaureate IRTA Fellow

  • Stacey Kigar
    Postdoctoral IRTA Fellow

  • Donghyun Kim
    Post baccalaureate IRTA Fellow

  • Michael Lehmann, Ph.D.
    Staff Scientist
    301-402-3243

  • Samuel Listwak, Ph.D.
    Research Chemist
    301-402-3132

  • Nicole Wrigley
    Post baccalaureate IRTA Fellow

  • 1) Lehmann M.L., Weigel T.K., Elkahloun A.G., Herkenham M. (2017)
  • Chronic social defeat reduces myelination in the mouse medial prefrontal cortex
  • Sci. Reports, 7: 46548
  • 3) Lehmann, M.L., Cooper, H.A., Maric, D., Herkenham, M (2016)
  • Social defeat induces depressive-like states and microglial activation without involvement of peripheral macrophages
  • J. Neuroimmunol, 13: 224
  • 4) Brachman, R.A., Lehmann, M.L., Maric, D., and Herkenham, M (2015)
  • Lymphocytes from chronically stressed mice confer antidepressant-like effects to naïve mice
  • J. Neurosci, 35, 1530-1538
  • 5) Lehmann, M.L., Brachman, R.A., Martinowich, K., Schloesser, R.J., and Herkenham, M (2013)
  • Glucocorticoids orchestrate divergent effects on mood through adult neurogenesis
  • J. Neurosci, 33, 2961-2972
  • 6) Listwak, S.J., Rathore, P., and Herkenham, M (2013)
  • Minimal NF-kB activity in neurons
  • Neuroscience, 250, 282-299
  • 7) Oskvig, D. B., Elkahloun, A. G., Johnson, K. R., Phillips, T. M. and Herkenham, M (2012)
  • 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
  • Brain, Behavior, Immun, 26, 623-634
  • 8) Schloesser, R.J., Lehmann, M., Martinowich, K., Manji, H.K., Herkenham, M (2010)
  • Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress
  • Mol. Psychiatry, 15, 1152-1163
  • 9) Chakravarty S, Herkenham M (2005)
  • Toll-like receptor 4 on non-hematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines
  • J. Neuroscience, 25, 1788-1796
  • 10) Quan, N., Whiteside, M., Kim, L. and Herkenham, M. (1997)
  • Induction of inhibitory factor kappaBalpha mRNA in the central nervous system after peripheral lipopolysaccharide administration: an in situ hybridization histochemistry study in the rat
  • Proc. Natl. Acad. Sci., U S A, 94, 10985-90
  • 11) Lynn, A. B. and Herkenham, M (1994)
  • Localization of cannabinoid receptors and nonsaturable high density cannabinoid binding sites in peripheral tissues of the rat: implications for receptor-mediated immune modulation by cannabinoids
  • J. Pharmacol. Exp. Ther, 268, 1612-1623
  • 12) Hurd, Y. L. and Herkenham, M. (1993)
  • Molecular alterations in the neostriatum of human cocaine addicts
  • Synapse, 13, 357-369
  • 13) Brady, L. S., Whitfield, H. J. Jr., Fox, R. J., Gold, P. W., and Herkenham, M. (1991)
  • Long-term imipramine administration increases mineralocorticoid receptor mRNA in the hippocampus and decreases corticotropin-releasing hormone mRNA in the hypothalamus of rats
  • J. Clin. Invest, 87, 831-837
  • 14) Herkenham, M., Lynn, A. B., Little, M. D., Johnson, M. R., Melvin, L. S., de Costa, B. R., and Rice, K. C. (1990)
  • Cannabinoid receptor localization in brain
  • Proc. Natl. Acad. Sci. USA, 87, 1932-1936
  • 15) Herkenham, M. and Pert, C. B. (1981)
  • Mosaic distribution of opiate receptors, parafascicular projections and acetylcholinesterase in the rat striatum
  • Nature, 291, 415-418
  • 16) Lehmann, M.L., Brachman, R.A., Listwak, S.J., Herkenham, M (2010)
  • NF-kappaB activity affects learning in aversive tasks: possible actions via modulation of the stress axis
  • Brain Behav. Immun, 24, 1008-1017
  • 17) Bryceson Y, Foster J A, Kuppusamy SP, Herkenham M, Long EO (2005)
  • Expression of a killer cell receptor gene in plastic regions of the central nervous system
  • J. Neuroimmunology, 161, 177-182
  • 18) Kassed CA, Herkenham M (2004)
  • NF-kappaB p50-deficient mice show reduced anxiety-like behaviors in tests of exploratory drive and anxiety
  • Behav. Brain Res., 154, 577-584
  • 19) Foster JA, Puchowicz MJ, McIntyre DC, Herkenham M (2004)
  • Activin mRNA induced during amygdala kindling shows a spatiotemporal progression that tracks the spread of seizures
  • J. Comp. Neurol, 476, 91-102
  • 20) Proescholdt MG, Quigley L, Martin R, Herkenham M (2002)
  • Immunization with a cannabinoid receptor type 1 peptide results in experimental allergic meningo-cerebellitis in the Lewis rat: A model for cell-mediated autoimmune neuropathology
  • J. Neuroscience Research, 70, 150-160
  • 21) Proescholdt MG, Chakravarty S, Foster JA, Foti SB, Briley EM, Herkenham M (2002)
  • Intracerebroventricular but not intravenous interleukin-1b induces widespread vascular-mediated leukocyte infiltration and immune signal mRNA expression followed by brain-wide glial activation
  • Neuroscience, 112, 731–749
  • 22) Proescholdt, M. G., Hutto, B., Brady, L. S. and Herkenham, M. (2000)
  • Studies of cerebrospinal fluid flow and penetration into brain following lateral ventricle and cisterna magna injections of the tracer [14C]inulin in rat
  • Neuroscience, 95, 577-592
  • 23) Quan, N., He, L., Lai, W., Shen, T., and Herkenham, M. (2000)
  • Induction of IkappaBalpha mRNA expression in the brain by glucocorticoids: a negative feedback mechanism for immune-to-brain signaling
  • J. Neurosci., 20, 6473-6477
  • 24) Herkenham, M. (1999)
  • Extrasynaptic receptors and parasynaptic communication in the brain
  • Brain Res. Bull., 50, 351-352
  • 25) Hohmann, A. G. and Herkenham, M. (1999)
  • Localization of central cannabinoid CB1 receptor messenger RNA in neuronal subpopulations of rat dorsal root ganglia: a double-label in situ hybridization study
  • Neuroscience, 90, 923-931
  • 26) Quan, N., Whiteside, M. and Herkenham, M. (1998)
  • Time course and localization patterns of interleukin-1beta messenger RNA expression in brain and pituitary after peripheral administration of lipopolysaccharide
  • Neuroscience, 83, 281-293
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