The neostriatum, or striatum for short, is the largest of the basal ganglia nuclei, and its principal input structure. A large number of neurological and psychiatric diseases, including Parkinson’s Disease, Huntington’s Disease, Schizophrenia, Tourette Syndrome and others result from damage or dysfunction of basal ganglia pathways through or to the striatum.
Although more than 90% of striatal neurons are GABAergic spiny projection neurons, recent evidence suggests that some of the most important sources of intrastriatal GABAergic signaling is from the 5-10% of neurons that are GABAergic interneurons. These are the principal focus of our research.
In my lab we use transgenic mice that express fluorescent reporter proteins like EGFP and/or cell-specific Cre recombinase with viral transduction to visualize and control the activity of specific interneuronal subtypes expressing different markers, of which there are many. For example, striatal GABAergic interneurons can be subdivided into neurons that express parvalbumin, tyrosine hydroxylase, neuropeptide Y (NPY), somatostatin, calretinin and other neurochemicals. We use a combination of optogenetics, chemogenetics, whole cell recording in living brain slices and brightfield, fluorescence and confocal microscopy to study these different interneurons and the specific synaptic circuits that they make in the stratum. These experiments are intertwined with behavioral experiments that both inform and are informed by the results of the in vitro recording studies.
We are also interested in neurons that use the neurotransmitter, dopamine, that are located in the midbrain in the substantia nigra, another key basal ganglia nucleus. We use the same techniques described above to investigate the circuits that control the activity of dopaminergic neurons.
While most of the experiments in the lab are basic science experiments, we also use experimental animal models of certain human diseases including Parkinson’s Disease, Tourette Syndrome and Autism to see how basal ganglia structure and function are altered in these models, with the aim of seeking new avenues of therapy for human diseases.
The lab currently consists of 1 graduate student, 2 post-docs, a research associate and a technician. We are funded by NIH-NINDS who has funded us continuously from 1987-2018.
James M. Tepper earned his B.A. in psychology, and his M.A. and Ph.D. in biological psychology from the University of Colorado, Boulder. He performed his post-doctoral research at the University of California, San Diego, where he focused his work on the structure and function of the basal ganglia. He joined the Center for Molecular and Behavioral Neuroscience in 1987 as the first faculty member hired by Co-Directors Ian Creese and Paula Tallal, and in 2008 was appointed a distinguished professor by the Rutgers Board of Governors. He is a fellow of the prestigious American Association for the Advancement of Science and president of the International Basal Ganglia Society. He also is a skilled guitarist who has produced two CDs.