The deep cerebellar nuclei to striatum disynaptic connection contributes to skilled forelimb movement

• Published in: Cell reports (Cambridge) 2023-01, Vol.42 (1), p.112000-112000, Article 112000
• Main Authors: Contreras-López, Rubén, Alatriste-León, Hector, Díaz-Hernández, Edgar, Ramírez-Jarquín, Josué O., Tecuapetla, Fatuel
• Format: Article
• Language: English
• Subjects: Animals; Cerebellar Nuclei; Cerebellum; Corpus Striatum; CP: Neuroscience; deep cerebellar nuclei; disynapses; Forelimb; forelimbs; intralaminar nuclei; motor control; Movement; optogenetics; thalamo-striatal; Thalamus
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112000

Cerebellar-thalamo-striatal synaptic communication has been implicated in a wide range of behaviors, including goal-directed actions, and is altered in cerebellar dystonia. However, its detailed connectivity through the thalamus and its contribution to the execution of forelimb movements is unclear. Here, we use trans-synaptic and retrograde tracing, ex vivo slice recordings, and optogenetic inhibitions during the execution of unidirectional or sequential joystick displacements to demonstrate that the deep cerebellar nuclei (DCN) influence the dorsal striatum with a very high probability. We show that this mainly occurs through the centrolateral (CL), parafascicular (PF), and ventrolateral (VL) nuclei of the thalamus, observing that the DCN→VL and DCN→CL pathways contribute to the execution of unidirectional forelimb displacements while the DCN→PF and DCN→thalamo→striatal pathways contribute to the appropriate execution of forelimb reaching and sequential displacements. These findings highlight specific contributions of the different cerebellar-thalamo-striatal paths to the control of skilled forelimb movement. [Display omitted] •The DCN are connected with the striatum mainly through the CL, PF, and the VL•Inhibition of the DCN→thalamo→striatal or the DCN→PF projections impairs reaching•Inhibition of the DCN→VL and DCN→CL projections impairs unidirectional displacements•Inhibition of the DCN→Th→Str pathways impairs the execution of sequential displacements The deep cerebellar nuclei influence the striatal activity through the thalamus. Contreras-López et al. show that this communication occurs through the intralaminar and the ventral lateral thalamus. This disynaptic communication contributes to the execution of appropriate reaching and is required to execute sequential, but not unidirectional, skilled forelimb movements.