| | Principal Investigators
| Charles Gerfen,
Ph.D. |
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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 at 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 is currently the Chief
of the Laboratory of Systems Neuroscience at the NIMH. |
| Research Interests |
| Dr. Gerfen's research goals involve elucidating the functional organization of the basal ganglia. Specifically, the lab studies receptor mediated gene regulation, with an emphasis on how functionally defined neurons in the forebrain display distinct forms of neuronal plasticity. While the role of the basal ganglia in behavior remains elusive, diseases that affect its function result in profound neurological disorders, including movement disorders such as Parkinson's Disease, chorea, and dystonia, and mental disorders such as Attention Deficit Hyperactivity Disorder and Depression. 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. 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.
Dr. Gerfen is a co-Investigator on the Gene Expression Nervous System Atlas (GENSAT) project, with Nat Heintz at Rockefeller University. This project provides transgenic mouse lines to the neuroscience research community with neuron specific expression of Cre recombinase. Over 50 Cre-driver lines have been characterized with expression limited to specific neuron types or specific brain regions. Information and availability of these mice may be accessed through the GENSAT website.
Dr. Gerfen's research goals involve elucidating the functional organization of the basal ganglia. Specifically, the lab studies 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. While the role of the basal ganglia in behavior remains obscure, diseases that affect its function result in profound neurological disorders, including movement disorders such as Parkinson's Disease, chorea, and dystonia, and mental disorders such as Attention Deficit Hyperactivity Disorder and Depression. His 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. His 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. |
| Representative Selected Recent Publications: |
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Nadjar A, Gerfen CR, Bezard E. Priming for L-dopa-induced dyskinesia in Parkinson's disease: A feature inherent to the treatment of the disease? Prog Neurobiol. 87:1-9. 2009.
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Gerfen CR, Paletzki R, Worley PW. Differences between dorsal and ventral striatum in Drd1a-dopamine receptor coupling of DARPP-32 to activation of extracellular receptor kinase (ERK1/2). Journal of Neuroscience. 28:7113-7120. 2008.
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Gong S, Doughty M, Harbaugh CR, Cummins A, Hatten ME, Heintz N, Gerfen CR. Targeting CRE recombinase to specific neuron populations with Bacterial Artificial Chromosome constructs. Journal of Neuroscience. 27:9817-9823. 2007.
- Brown P and Gerfen CR. Plasticity within striatal direct pathway neurons following neonatal dopamine depletion is mediated through a novel functional coupling of serotonin 5-HT2 receptors to the ERK1/2/MAP Kinase pathway. J Comp Neurol. 498:415-430. 2006.
- Gerfen CR, Miyachi S, Paletzki R, Brown P:
D1 dopamine receptor supersensitivity in the dopamine-depleted striatum results from a switch in the regulation of ERK1/2/MAP kinase.
Journal of Neuroscience, 22: 5042-5054, 2002. (View PDF)
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