Principal Investigator: Miles Herkenham
Section on Functional Neuroanatomy
Laboratory of Cellular and Molecular Regulation
Dr. Herkenham received a B.A. degree 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 and the beneficial effects of environmental enrichment, and immune signal molecule induction and function in the developing and adult brain.
Our group uses the tools of modern neuroanatomy to investigate nervous system regulatory events that occur in animals when they respond and adapt to immune challenges, drug administration, emotional challenges, psychosocial stress, or environmental enrichment. Responsive brain structures and cell types are identified by in situ hybridization histochemistry, immunohistochemistry, cell sorting, and assays for protein and gene expression profiles. Behavior is characterized in validated tests for anxiety- and depressive-like states and social interactions. We use DNA microarray; knockout, transgenic, and reporter mice; bone marrow cells in chimeras; and viral-based delivery of DNA constructs to limbic system targets. Recent work examines the causal relationships amongst the depressive states produced by social defeat and the restorative or preventative effects of environmental enrichment combined with circuitry analysis of responsive brain regions and the assessment of roles played by adult neurogenesis and elevated adrenal hormones. These types of paradigms guide further cellular work aimed at understanding the molecular and biochemical bases for altered emotionality.
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. Oskvig DB, Elkahloun AG, Johnson KR, Phillips TM, Herkenham M. Brain Behav Immun. 2012 May;26(4):623-34. doi: 10.1016/j.bbi.2012.01.015. Epub 2012 Jan 30. PMID: 22310921.
Environmental enrichment confers stress resiliency to social defeat through an infralimbic cortex-dependent neuroanatomical pathway. Lehmann ML, Herkenham M. J Neurosci. 2011 Apr 20;31(16):6159-73. doi: 10.1523/JNEUROSCI.0577-11.2011. PMID: 21508240.
Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress. Schloesser RJ, Lehmann M, Martinowich K, Manji HK, Herkenham M. Mol Psychiatry. 2010 Dec;15(12):1152-63. doi: 10.1038/mp.2010.34. Epub 2010 Mar 23. PMID: 20308988.
NF-kappaB activity affects learning in aversive tasks: possible actions via modulation of the stress axis. Lehmann ML, Brachman RA, Listwak SJ, Herkenham M. Brain Behav Immun. 2010 Aug;24(6):1008-17. doi: 10.1016/j.bbi.2010.04.005. Epub 2010 Apr 23. PMID: 20399847.
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