Motor skills mediated through cerebellothalamic tracts projecting to the central lateral nucleus

Abstract

The cerebellum regulates complex animal behaviors, such as motor control and spatial recognition, through communication with many other brain regions. The major targets of the cerebellar projections are the thalamic regions including the ventroanterior nucleus (VA) and ventrolateral nucleus (VL). Another thalamic target is the central lateral nucleus (CL), which receives the innervations mainly from the dentate nucleus (DN) in the cerebellum. Although previous electrophysiological studies suggest the role of the CL as the relay of cerebellar functions, the kinds of behavioral functions mediated by cerebellothalamic tracts projecting to the CL remain unknown. Here, we used immunotoxin (IT) targeting technology combined with a neuron-specific retrograde labeling technique, and selectively eliminated the cerebellothalamic tracts of mice. We confirmed that the number of neurons in the DN was selectively decreased by the IT treatment. These IT-treated mice showed normal overground locomotion with no ataxic behavior. However, elimination of these neurons impaired motor coordination in the rotarod test and forelimb movement in the reaching test. These mice showed intact acquisition and flexible change of spatial information processing in the place discrimination, Morris water maze, and T-maze tests. Although the tract labeling indicated the existence of axonal collaterals of the DN-CL pathway to the rostral part of the VA/VL complex, excitatory lesion of the rostral VA/VL did not show any significant alterations in motor coordination or forelimb reaching, suggesting no requirement of axonal branches connecting to the VL/VA complex for motor skill function. Taken together, our data highlight that the cerebellothalamic tracts projecting to the CL play a key role in the control of motor skills, including motor coordination and forelimb reaching, but not spatial recognition and its flexibility.

Dual contributions of cerebellar-thalamic networks to learning and offline consolidation of a complex motor task

“…indeed, the selective ablation of Dentate-CL neurons has been reported to yield locomotor deficits in the initial performances on the accelerated rotarod (Sakayori et al, 2019), which contrasts with the lack of significant deficit in the Acquisition phase following Dentate-CL (partial) inhibition in our study. A possible explanation could be that our intervention selectively disrupted the advanced patterns of locomotion only needed at the higher speeds of the rotarod.…”

“…The inhibition of Interposed-VAL neurons during the task also yield lower levels of performance in the Maintenance stage, suggesting that these neurons contribute also to learning and retrieval of motor skills, although the mild defect in fixed speed rotarod could indicate the presence of an execution problem. Interestingly, both Dentate and Interposed nuclei contain some neurons with collaterals in both thalamic structures (Aumann and Horne, 1996;Sakayori et al, 2019), suggesting that the effect on learning could be mediated in part by a combined action on the learning process of the striatum (via the CL thalamus) and cortex (via the VAL thalamus); however, consistent with (Sakayori et al, 2019), the manipulations of cerebellar neurons retrogradely targeted either from the CL or from the VAL produce different effects.…”

Deleting Mecp2 from the cerebellum rather than its neuronal subtypes causes a delay in motor learning in mice

“…In addition to the cerebellum, multiple brain regions including the cortex and basal ganglia contribute to motor learning on the rotarod ( Sakayori et al, 2019 ). Therefore, we used eyeblink conditioning, an alternate task of motor learning for which the cerebellum is strictly necessary, to validate the motor learning deficits observed in cerebellar KO mice ( Figure 2D ; Heiney et al, 2014 ).…”

Transcranial Direct Current Stimulation to Facilitate Lower Limb Recovery Following Stroke: Current Evidence and Future Directions

“…It is noteworthy that a computational modelling study that compared electrode montages targeting M1 and the cerebellum found that cerebellar stimulation produced substantially higher electric field strengths in the target area compared to M1 stimulation, suggesting the cerebellum may indeed be a suitable target for tDCS [38]. Behaviorally, the cerebellum contributes to motor planning, learning, and control; this influence is in part mediated by connections to M1 via the cerebellothalamocortical tracts, previously reported to play a key role in motor skill learning in mice [39]. Although this stimulation technique has received comparatively little attention compared to M1 stimulation, there is some indication that it is possible to modify cerebellar excitability in a focal and polarity specific manner [40].…”