Aryn H. Gittis
116D Mellon Institute
Department of Biological Sciences
Carnegie Mellon University
4400 Fifth Avenue
Pittsburgh, PA 15213
Ph.D., University of California, San Diego
Postdoctoral Appointment, Gladstone Institute for Neurological Disease
How do neural circuits transform our thoughts into actions? I study neural circuits in the basal ganglia, a multifunctional brain region that plays a role in the regulation of movement, learning, motivation, and reward. My specific interests include how neural circuits in the basal ganglia are altered by experience and why certain circuits breakdown in movement disorders such as Parkinson’s disease and dystonia. My 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. There are two main interests in the lab:
- What causes neural circuits in the basal ganglia to become synchronized and locked into pathological oscillations in movement disorders such as Parkinson’s disease? The external segment of the globus pallidus (GPe) is a central nucleus in the basal ganglia where dramatic changes in neuronal firing patterns are observed after loss of dopamine. Understanding how these pathological firing patterns develop and propagate throughout the basal ganglia is a critical step towards developing better treatments for movement disorders. In canonical models of basal ganglia function, the GPe communicates with the rest of the basal ganglia through the subthalamic nucleus. However, the GPe makes direct projections to a number of other basal ganglia nuclei and alterations in these projections have the potential to cause widespread disruption of basal ganglia function. Using transgenic mouse lines to identify and control the activity of distinct cell types within the GPe, we seek to understand the organization and function of neural circuits within the GPe and how changes to these circuits participate in learning, motor control, and movement disorders such as Parkinson’s disease.
- How are sensory and motor information integrated in the basal ganglia and how is this altered by experience? Although the basal ganglia are primarily thought of as a motor system, they receive inputs from many parts of cortex, including sensory areas. Both motor and sensory inputs to the striatum, a major input nucleus to the basal ganglia, display a topographical organization. How these two sources of information are integrated at the level of single neurons is not well understood. We are interested in how changes in sensory inputs, achieved by whisker plucking, affect neural circuit organization within the striatum and how plasticity of sensory representations interacts with motor representations. To address these questions, we use targeted injections of dyes, optogenetic, and pharmacogenetic constructs to label and manipulate anatomically specific pathways in the striatum. Aberrant plasticity in anatomically specific sensory/motor pathways in the striatum may play a role in the development of some forms of dystonia and other basal ganglia related disorders.
Mastro KJ, Gittis AH. Striking the right balance: cortical modulation of the subthalamic nucleus-globus pallidus circuit. Neuron. 2015 Jan 21;85(2):233-5.
Gittis AH, Berke JD, Bevan MD, Chan CS, Mallet N, Morrow MM, Schmidt R. New roles for the external globus pallidus in Basal Ganglia circuits and behavior. J Neurosci. 2014 Nov 12;34(46):15178-83.
Mastro KJ, Bouchard RS, Holt HA, Gittis AH. Transgenic mouse lines subdivide external segment of the globus pallidus (GPe) neurons and reveal distinct GPe output pathways. J Neurosci. 2014 Feb 5;34(6):2087-99.
Gittis AH, Kreitzer AC. Striatal microcircuitry and movement disorders. Trends Neurosci. 2012 Jul 31.
Gittis AH, Leventhal, DK, Fensterheim BA, Pettibone JR, Berke JD, Kreitzer AC. Selective inhibition of striatal fast-spiking interneurons causes dyskinesia. J Neurosci. 2011 Nov 2;31(44):15727-31.
Gittis AH, Hang GB, Shoenfeld LM, Atallah B, Kreitzer A. Rapid reorganization of striatal microcircuits in a mouse model of Parkinson’s disease. Neuron 71(5): 858-868.
Higley MJ, Gittis AH, Oldenburg IA, Balthasar N, Seal RP, Edwards RH, Lowell BB, Kreitzer AC, Sabatini BL. Cholinergic interneurons mediate fast VGluT3-dependent glutamatergic transmission in the striatum. PLoS One. 2011 Apr 22;6(4):e19155.