Role of synchronous activation of cerebellar Purkinje cell ensembles in multi-joint movement control

It is a longstanding question in neuroscience how elaborate multi-joint movements are coordinated coherently. Microzones of cerebellar Purkinje cells (PCs) are thought to mediate this coordination by controlling the timing of particular motor domains. However, it remains to be elucidated to what ext...

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Published in:Current biology 2015-05, Vol.25 (9), p.1157-1165
Main Authors: Hoogland, Tycho M., De Gruijl, Jornt R., Witter, Laurens, Canto, Cathrin B., De Zeeuw, Chris I.
Format: Article
Language:eng
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Summary:It is a longstanding question in neuroscience how elaborate multi-joint movements are coordinated coherently. Microzones of cerebellar Purkinje cells (PCs) are thought to mediate this coordination by controlling the timing of particular motor domains. However, it remains to be elucidated to what extent motor coordination deficits can be correlated with abnormalities in coherent activity within these microzones and to what extent artificially evoked synchronous activity within PC-ensembles can elicit multi-joint motor behavior. To study PC ensemble correlates of limb, trunk and tail movements we developed a transparent disk-treadmill that allows quantitative read-out of locomotion and posture parameters in head-fixed mice and simultaneous cellular-resolution imaging and/or optogenetic manipulation. We show that PC ensembles in the ataxic and dystonic mouse mutant tottering have a reduced level of complex spike co-activation, which is delayed relative to movement onset and co-occurs with prolonged swing duration and reduced phase-coupling of limb movements as well as with enlarged deflections of body-axis and tail movements. Using optogenetics to increase simple spike rate in PC-ensembles, we find that preferred locomotion and posture patterns can be elicited or perturbed depending on the behavioral state. At rest, preferred sequences of limb movements can be elicited, whereas during locomotion preferred gait inhibition patterns are evoked. Our findings indicate that synchronous activation of PC-ensembles can facilitate initiation and coordination of limb and trunk movements, presumably by tuning downstream systems involved in the execution of behavioral patterns. -Tg/tg mice show affected swing duration and phase-coupling of limb movements.-PCs in ataxic tg/tg mice show delayed and reduced complex spike (CS) co-activation.-At rest, simple spike (SS) co-activation can elicit preferred locomotion sequences.-During locomotion, SS co-activation can be correlated with gait inhibition patterns.
ISSN:0960-9822
1879-0445