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Senior Investigator

Charles R. Gerfen, Ph.D.


Building 35 Room 3A-1000
35 Convent Drive MSC 3726
Bethesda MD 20892-3726
Office: (301) 496-4341

Fax: (301) 402-8960
gerfenc@intra.nimh.nih.gov

Dr. Gerfen received a B.A. from Amherst College and Ph.D. from Northwestern University. His doctoral research was on neural substrates of reward involving the prefrontal cortex and basal ganglia. During a post-doctoral fellowship in the Laboratory of Max Cowan at the Salk Institute, he developed the PHA-L axonal tracing technique with Paul Sawchenko. In 1983, Dr. Gerfen was recruited by Ed Evarts to the Laboratory of Neurophysiology within NIMH to work on the neuroanatomy of the forebrain and established some of the functional prinicples of the organization of the basal ganglia. Dr. Gerfen's lab now works on receptor mediated gene regulation, with an emphasis on how functionally defined neurons in the forebrain display distinct forms of neuronal plasticity, dependent on differential regulation of multiple protein kinase signaling pathways.



We study the functional organization of the basal ganglia. While the role of the basal ganglia in behavior remains obscure, diseases that affect its function result in profound neurological disorders, including Parkinson's Disease, chorea, dystonia and other movement disorders, and is implicated in a wide range of mental disorders including Attention Deficit Hyperactivity Disorder and Depression. Our research initially mapped out the connectional organization of this system, characterizing the compartmental nature of the input-output organization of the striatum, which is the main nucleus of the basal ganglia. This work identified the principal neuron types in the basal ganglia in terms of their neuroanatomical connections and neurochemical phenotype. Our work is now focused on how the two main output neurons of the striatum, direct and indirect projection neurons, differ functionally, through their distinct responses to glutamatergic excitatory inputs as modulated by their expression of D1 and D2 dopamine receptor subtypes. Current work examines differences in receptor-mediated signal transduction regulation of the gene expression underlying distinct forms of neuronal plasticity in direct and indirect striatal projection neurons. Particular emphasis is placed on determining the molecular basis of an aberrant form of neuronal plasticity that occurs in direct projection neurons in animal models of Parkinson's disease.

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  • Subhadra Banerjee, Ph.D.
    Research Fellow
    (301) 402-6888

  • Pierre Brown, Ph.D.
    Postdoctoral Fellow
    (301) 402-6948

  • Alex Cummins
    Senior Research Assistant

  • Ron Harbaugh
    Senior Research Assistant
    (301) 496-9334

  • Hui-Min Zhao, Ph.D.
    Research Fellow
    (301) 402-6826

  • 1) Gerfen CR, Miyachi S, Paletzki R, Brown P (2002)
  • D1 Dopamine receptor supersensitivity in the dopamine-depleted striatum results from a switch in the regulation of ERK1/2/MAP Kinase
  • J Neuroscience, 22, 5042-5054
  • 2) Keefe KA, Gerfen CR (1999)
  • Local infusion of the AMPA/kainate receptor antagonist CNQX does not block D1 dopamine receptor-mediated increases in immediate early gene expression in the dopamine-depleted striatum.
  • Neuroscience, 89, 491-504
  • 3) Steiner H, Gerfen CR (1998)
  • Enkephalin regulates acute D2 dopamine receptor antagonist-induced immediate-early gene expression in striatal neurons.
  • Neuroscience, 88, 795-810
  • 4) Berke JD, Paletzki RF, Aronson GJ, Hyman SE, Gerfen CR (1998)
  • A complex program of striatal gene expression induced by dopaminergic stimulation
  • J Neuroscience, 18, 5301-5310
  • 5) Steiner H, Gerfen CR (1996)
  • Dynorphin regulates D1 dopamine receptor-mediated responses in the striatum: relative contributions of pre- and postsynaptic mechanisms in dorsal and ventral striatum demonstrated by altered immediate-early gene induction
  • J. Comparative Neurology, 376, 530-41
  • 6) Gerfen CR, KA Keefe, EB Gauda (1995)
  • D1 and D2 dopamine receptor function in the striatum: Co-activation of D1- and D2-dopamine receptors on separate populations of neurons results in potentiated immediate early gene response in D1-containing neurons.
  • J. Neuroscience, 15, 8167-8176
  • 7) Gerfen, CR et al (1990)
  • D1 and D2 dopamine receptor mediated regulation of gene expression in striatonigral and striatopallidal pathways
  • Science, 250, 1429-1432
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