Cerebellar nuclei evolved by repeatedly duplicating a conserved cell-type set

Abstract

Cerebellar evolution Cerebellar nuclei, substructures of the cerebellum, transfer information from the cerebellum to other parts of the brain. Using single-cell transcriptomics, Kebschull et al. have now identified a conserved pattern of cerebellar nuclei structure that has been repeated through evolution (see the Perspective by Hatten). Ranging from mice to chickens to humans, cerebellar nuclei are made up of region-specific excitatory neurons and region-invariant inhibitory neurons. In humans, a facet connecting the cerebellum to the frontal cortex is enhanced. Science , this issue p. eabd5059 ; see also p. 1411

Transcriptome programs involved in the development and structure of the cerebellum

“…Cerebellar nuclei derive from the coordinated integration in the nuclear transitory zone of glutamatergic and large glycinergic projection neurons migrating from the RL, and of GABAergic interneuron precursors migrating from the VZ [10]. The development of glutamatergic projection neurons depends on OLIG3 expression [58] and on differential expression of PAX6, T-Box Brain Transcription Factor 1 (TBR1) and LIM Homeobox Transcription Factor 1 Alpha (LMX1A) in the medial cerebellar nuclei, or OLIG2 and LHX9 in the lateral cerebellar nuclei [47].…”

“…Notably, cerebellar nuclei also receive excitatory inputs from collaterals of both parallel and climbing fibers and send feedback signals to the inferior olive, thus fine tuning the final output of the cerebellar circuitry [ 9 ]. Cerebellar nuclei display a complex cytoarchitectural structure, wherein glutamatergic, GABAergic and glycinergic neurons are stereotypically arranged in functionally distinct subunits [ 9 , 10 ].…”

Recent Advances in the Understanding of Specific Efferent Pathways Emerging From the Cerebellum

“…Indeed, beyond the traditional cerebellar functions in supervised motor learning utilizing prediction error, lines of evidence suggest that the cerebellar network machinery is widely involved in the processing, generating, and testing of motor and non-motor predictions ( Sokolov et al, 2017 ; Popa and Ebner, 2018 ; Hull, 2020 ). Furthermore, it has been shown that the cerebellum makes broad projections to multiple brain regions through both direct and indirect pathways ( Kebschull et al, 2020 ). Thus, specific anatomical efferent connections appear to at least be partly responsible for specific cerebellar functions.…”

“…All three nuclei of the DCN are embedded in the deep central area of the cerebellum. Even though DCN neurons in general project to a broad area, the overall projecting targets from each nucleus have different characteristics ( Teune et al, 2000 ; Kebschull et al, 2020 ), such as more projections to the brainstem from the FN and more projections to the thalamus or midbrain from the IPN or DN. The anterior and posterior IPNs were also shown to have different projecting patterns ( Teune et al, 2000 ; Lu et al, 2012 ).…”

“…This suggests that each nucleus contributes to distinct functions. Detailed analyses further demonstrated different projection patterns from distinct groups of neurons in the same nucleus ( Fujita et al, 2020 ; Kebschull et al, 2020 ). Heterogeneity in the electrophysiological and anatomical properties has also been reported in DCN neurons ( Czubayko et al, 2001 ; Aizenman et al, 2003 ; Sultan et al, 2003 ; Uusisaari and Knöpfel, 2012 ; Canto et al, 2016 ), although their functional relevance is not completely understood.…”