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. 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. 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.
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.
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