Disrupted basal ganglia output during movement preparation in hemi-parkinsonian mice accounts for behavioral deficits

Abstract

AbstractParkinsonian motor deficits are associated with elevated inhibitory output from the basal ganglia (BG). However, several features of Parkinson’s disease (PD) have not been accounted for by this simple “rate model” framework, including the observation in PD patients that movements guided by external stimuli are less impaired than otherwise-identical movements generated based on internal goals. Is this difference in impairment due to divergent processing within the BG itself, or to the recruitment of extra-BG pathways by sensory processing? In addition, surprisingly little is known about precisely when, in the sequence from selecting to executing movements, BG output is altered by PD. Here, we address these questions by recording activity in the SNr, a key BG output nucleus, in hemiparkinsonian (hemi-PD) mice performing a well-controlled behavioral task requiring stimulus-guided and internally-specified directional movements. We found that hemi-PD mice exhibited a bias ipsilateral to the side of dopaminergic cell loss that was stronger when movements were internally specified rather than stimulus guided, consistent with clinical observations in parkinsonian patients. We further found that changes in parkinsonian SNr activity during movement preparation could account for the ipsilateral behavioral bias, as well as its greater magnitude for internally-specified movements, consistent with some aspects of the rate model. These results suggest that parkinsonian changes in BG output underlying movement preparation contribute to the greater deficit in internally-specified than stimulus-guided movements.