Neural responses in multiple basal ganglia regions following unilateral dopamine depletion in behaving rats performing a treadmill locomotion task

To investigate basal ganglia (BG) neural responses to dopamine (DA) depletion, multiple channel, single unit recording was carried out in freely moving rats performing a treadmill locomotion task. Single unit activity from 64 microelectrodes in the striatum (STR), globus pallidus (GP), subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) was recorded simultaneously before and after a unilateral DA lesion induced by microinjection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. The DA lesion resulted in an impairment of treadmill walking manifested by a significant decrease in swing time of both forelimbs. The stance time, however, increased significantly only in ipsilateral (good) forelimbs, reflecting compensatory changes in the good limb for motor deficits. Neural activity in the STR and GP ipsilateral to the lesion decreased during the 7-day period following the DA lesion. Conversely, an increase in spike discharges appeared in the ipsilateral SNr and STN several days after the DA lesion. Changes in the type of neural response associated with treadmill locomotion were also found in some neurons after DA depletion. Such changes were most prominent in the STR. Limb movement-related neural activity increased significantly mainly in the SNr. Additionally, neural responses to the tone cue associated with the onset of the treadmill diminished greatly in the lesioned side of the BG. Increased activity in SNr neurons is consistent with the concept that inhibition of thalamus contributes to hypokinesis in the absence of DA. Substantial decrease in striatal activity supports a concept that DA loss leads to a global suppression of recurrent cortical striatal thalamic activity that degrades normal information flow in Parkinson's diseases.