Movement- and drug-induced changes in the activity of basal ganglia output neurons in awake, unrestrained rats

The basal ganglia are a collection of brain nuclei known to be among the central nervous system structures that control movement. Classic theories of their function in motor behavior, which have been influenced most by the clinical literature on movement disorders and by animal models of basal ganglia-specific motor dysfunctions, have emphasized their role as a facilitator of desired motor actions through a release of their usually constant inhibition of "downstream" motor targets. An alternative approach to understand basal ganglia function, which is described in this dissertation, is the analysis of neuronal activity in animals actively engaged in motor tasks. Rats were placed in an operant behavior chamber and trained to produce nosepoke responses for access to a sucrose solution. After training, they were implanted with microelectrodes that allowed the recording of electrophysiological activity in the substantia nigra pars reticulata (SNr), the primary output nucleus of the rat basal ganglia. In a separate group of rats, SNr activity was recorded while animals were behaving in an open-field arena before and after systemic injection or intrastriatal infusion of amphetamine, a stimulant drug that produces dose-dependent increases in motor behavior. In animals trained in the nosepoke task, SNr neurons were found to change activity during specific behavioral events, such as a nosepoke or licking at a spout through which a sucrose solution was delivered. In contrast to the predictions of classic theories of basal ganglia function, these changes most often consisted of increases in SNr firing rate. Injection or striatal infusion of amphetamine, which led to robust behavioral activation, produced variable changes in firing rate, including a significant proportion of neurons that were unaltered relative to control values. The results presented in this dissertation support recent theories of basal ganglia function that emphasize both decreases in basal ganglia output as a means for selecting appropriate motor programs and increases in output serving to inhibit competing motor programs.