Neural circuits in the basal ganglia involved in motor control and disease
How do neural circuits transform our thoughts into actions? Our research focuses on neural circuits in the basal ganglia, a multifunctional brain region that plays a role in the regulation of movement, learning, motivation, and reward. We are interested in how basal ganglia circuits are altered by experience and why some circuits breakdown in movement disorders such as Parkinson’s disease, dystonia, and OCD. Our laboratory uses a variety of techniques including electrophysiology, optogenetics, histology, and behavior. We use mice as a model organism to understand how activity of specific basal ganglia circuits relates to motor control in both health and in animal models of movement disorders.
Our current work focuses on two main questions. First, what are the synaptic changes that occur in different cell populations within the external segment of the globus pallidus (GPe) under conditions of low dopamine? Using transgenic mouse lines to identify and control the activity of distinct cell types, we are studying the organization and function of neural circuits in the GPe and their ability to restore motor function in dopamine-depleted mice. Second, under chronic conditions of low dopamine (weeks to months), what mechanisms of compensatory plasticity occur and do they ameliorate motor control or contribute to its deterioration? To address this questions, we combine behavioral experiments with slice and in vivo electrophysiology to identify altered activity in the basal ganglia and other brain areas involved in motor control.
Gittis, A.H. and Kreitzer, A.C. Striatal microcircuitry and movement disorders. Trends Neurosci Sep;35(9):557-64, 2012
Gittis, A.H., Leventhal, D.K., Fensterheim, B.A., Pettibone, J.R., Berke, J.D. and Kreitzer, A.C. Selective inhibition of striatal fast-spiking interneurons causes dyskinesia. J Neurosci. Nov 2; 31(44): 15727-31, 2011.
Gittis, A.H., Hang, G.B., Shoenfeld, L.M., Atallah, B. and Kreitzer, A. Rapid reorganization of striatal microcircuits in a mouse model of Parkinson’s disease.Neuron. 71(5): 858-868, 2011.
Higley, M.J., Gittis, A.H., Oldenburg, I.A., Balthasar, N., Seal, R.P., Edwards, R.H., Lowell, B.B., Kreitzer, A.C. and Sabatini, B.L. Cholinergic interneurons mediate fast VGluT3-dependent glutamatergic transmission in the striatum. PLoS One. 2011 Apr 22; 6(4):e19155.
Gittis, A.H., Nelson, A.B. and Kreitzer, A.C. Distinct roles of GABAergic interneurons in the regulation of striatal output pathways. J. Neurosci. Feb 10; 30(6):2223-34, 2010.