PT  - JOURNAL ARTICLE
AU  - Anand Tekriwal
AU  - Mario J. Lintz
AU  - John A. Thompson
AU  - Gidon Felsen
TI  - Disrupted basal ganglia output during movement preparation in hemi-parkinsonian mice accounts for behavioral deficits
AID  - 10.1101/2020.06.19.160457
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.19.160457
4099  - http://biorxiv.org/content/early/2020/06/20/2020.06.19.160457.short
4100  - http://biorxiv.org/content/early/2020/06/20/2020.06.19.160457.full
AB  - 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.Significance Statement Parkinsonian patients exhibit the intriguing phenomenon that movements guided by external stimuli are often less impaired than otherwise-identical movements generated based on internal goals. For example, patients can exhibit a more normal gait when their steps are guided by patterned floor tiling than when traversing a featureless floor. Whether this difference in movement execution is due to distinct processing intrinsic to the basal ganglia (BG) or to compensation from other motor pathways is an open question with therapeutic implications. We addressed this question by recording BG output during behavior in a parkinsonian mouse model. We found that mice exhibited greater impairment in internally-specified than stimulus-guided movements, and that differences in BG output during movement preparation could account for this effect.Competing Interest StatementThe authors have declared no competing interest.