Extrastriatal Dopaminergic Circuits of the Basal Ganglia

Lesioning and psychopharmacological studies suggest a wide range of behavioral functions for ascending midbrain dopaminergic systems. However, electrophysiological and neurochemical studies during specific behavioral tasks demonstrate a more restricted spectrum of dopamine-mediated changes. Substantial increases in dopamine-mediated activity, as measured by electrophysiology or voltammetry, are related to rewards and reward-predicting stimuli. A somewhat slower, distinct electrophysiological response encodes the uncertainty associated with rewards. Aversive events produce different, mostly slower, electrophysiological dopamine responses that consist predominantly of depressions. Additionally, more modest dopamine concentration fluctuations, related to punishment and movement, are seen at 200-18,000 times longer time courses using voltammetry and microdialysis in vivo. Using these responses, dopamine neurotransmission provides differential and heterogeneous information to subcortical and cortical brain structures about essential outcome components for approach behavior, learning and economic decision-making.

How the motor-related cortical areas modulate the activity of the output nuclei of the basal ganglia is an important issue for understanding the mechanisms of motor control by the basal ganglia. The cortico-subthalamo-pallidal 'hyperdirect' pathway conveys powerful excitatory effects from the motor-related cortical areas to the globus pallidus, bypassing the striatum, with shorter conduction time than effects conveyed through the striatum. We emphasize the functional significance of the 'hyperdirect' pathway and propose a dynamic 'center-surround model' of basal ganglia function in the control of voluntary limb movements. When a voluntary movement is about to be initiated by cortical mechanisms, a corollary signal conveyed through the cortico-subthalamo-pallidal 'hyperdirect' pathway first inhibits large areas of the thalamus and cerebral cortex that are related to both the selected motor program and other competing programs. Then, another corollary signal through the cortico-striato-pallidal 'direct' pathway disinhibits their targets and releases only the selected motor program. Finally, the third corollary signal possibly through the cortico-striato-external pallido-subthalamo-internal pallidal 'indirect' pathway inhibits their targets extensively. Through this sequential information processing, only the selected motor program is initiated, executed and terminated at the selected timing, whereas other competing programs are canceled.