November 30, 2020

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

Parkinsonian 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 supra-inhibition framework, including the potentially therapeutically-relevant observation that movements guided by external stimuli are less impaired than otherwise-identical movements generated based on internal goals. Is this difference 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 (n = 5, male) exhibited a bias ipsilateral to the side of dopaminergic cell loss, consistent with supra-inhibition of contralateral movements by BG output, and that this bias was stronger when movements were internally specified rather than stimulus guided, consistent with clinical observations in parkinsonian patients. We further found that changes in SNr activity during movement preparation could account for the ipsilateral behavioral bias, as well as its greater magnitude for internally-specified movements. These results suggest that parkinsonian changes in BG output underlying movement preparation contribute to the greater deficit in internally-specified in comparison to stimulus-guided movements.

 bioRxiv Subject Collection: Neuroscience

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