The basal ganglia are critically involved in the organization of motor behavior and sensorimotor integration. Malfunctions of this system in humans contribute to the pathophysiology of neuropsychiatric disorders such as schizophrenia and obsessive compulsive disorder, as well as to neurological diseases such as Huntington's and Parkinson's disease. Understanding the information processing within this system in mechanistic terms requires the understanding of the physiological properties and anatomical organization of the microcircuitry of its constituent nuclei. The neostriatum, the largest nucleus of the basal ganglia has a central role in controlling the functioning of the basal ganglia and therefore, an understanding of the intrinsic operations of this nucleus is critical to understanding information processing in the basal ganglia. Recently, it has been increasingly recognized that the quantitatively minor population of GABAergic interneurons of the neostriatum may play a critical role in the organization of the population activity of the principal cells. However, until the recent introduction of visually guided whole cell recording these neurons were not accessible for physiological investigation. In the proposed study, this powerful technology will be used in combination with intracellular staining and light and electron microscopic analysis to analyze the role of these interneurons in the control of the activity of their principal postsynaptic targets, the medium spiny neuron. Simultaneous paired recordings will be obtained from interneurons and medium spiny cells and the neurons will be stained for further anatomical investigation. The following specific questions will be addressed. First, what is the nature of the synaptic interaction between the two major types of inhibitory inteneurons and the medium spiny neuron? Second, what are the physiological and anatomical specializations of the inhibitory inputs to the medium spiny neuron from different types of interneurons? Third, what is the pattern of connectivity among the populations of interneurons and medium spiny neurons (i.e. convergence and divergence)? Finally, what are the physiological properties of electrical coupling between interneurons, a potentially significant mechanism affecting the population activity of these cells, as well as, the medium spiny neurons? This data will help in understanding the contribution of these interneurons to the organization of activity in the neostriatum.
| Koos, Tibor; Tepper, James M (2002) Dual cholinergic control of fast-spiking interneurons in the neostriatum. J Neurosci 22:529-35 |
| Koos, T; Tepper, J M (1999) Inhibitory control of neostriatal projection neurons by GABAergic interneurons. Nat Neurosci 2:467-72 |
