The goal of this project is to understand the neuronal mechanisms of the basal ganglia that mediate sequences of behavior. Studies in humans indicate that sequence control, especially the control of movement sequences, may be a fundamental property of the basal ganglia. Motor disorders of the basal ganglia, such as Parkinson's disease and Huntington's disease, are associated with a profound loss of the ability to organize and execute sequences of movement. Furthermore, cognitive disorders of the basal ganglia such as the uncontrollable repetition of spoken words in Tourette's syndrome and the tormenting habits and thoughts of obsessive compulsive disorder suggest that sequential control mechanisms may be a fundamental property of the basal ganglia. In this project, the correlates and properties of single neurons related to instinctive, stereotyped sequences of behavioral actions will be studied. The long term goals of this project are designed to answer the following questions: How does the brain and in particular, the basal ganglia coordinate behavioral sequences? Are there basic principals for sequential organization? What are the computational properties of sequence-related neuronal assemblies in the basal ganglia? A key hypothesis to be tested in this study is that neuronal activity of a subset of cells in the basal ganglia will be related to movements within the context of rule-governed behavioral sequences and not related to these movements when they occur on their own or in irregular, less organized sets of movements. Previous experiments have shown that rats exhibit highly structured (i.e., syntactical) sequences of grooming bouts that follow strict rules for their temporal organization and that these syntactical sequences are disrupted by damage to the basal ganglia. Rats also execute comparable grooming movements in isolation and in other randomly organized patterns of movements. Our method will be to record and compare the activity of single neurons in rats during both syntactical and non-syntactical grooming sequences. It is anticipated that neuronal activity will be preferentially linked to movements in the context of stereotyped syntactical sequences. We will evaluate the anatomical location of neurons related to grooming movements to test the idea that the functional organization is related to the proposed cortico-striatal loops in the basal ganglia. We will evaluate the hypothesis that neostriatal neurons mediate sequences by modulating sensorimotor responsiveness. Finally, we will test the idea that Dl dopamine receptor activation will enhance neuronal activity related to sequential movements and the dopaminergic lesions will produce the opposite effect. It is hoped that new information about the neuronal network properties related to the organization of behavioral sequences will lead to a better understanding of the pathophysiology of basal ganglia diseases and eventually contribute to better treatments for these brain disorders.
