Homologous organization of cerebellar pathways to sensory, motor, and associative forebrain

Abstract

SUMMARY Cerebellar outputs take polysynaptic routes to reach the rest of the brain, impeding conventional tracing. Here, we quantify pathways between the cerebellum and forebrain by using transsynaptic tracing viruses and a whole-brain analysis pipeline. With retrograde tracing, we find that most descending paths originate from the somatomotor cortex. Anterograde tracing of ascending paths encompasses most thalamic nuclei, especially ventral posteromedial, lateral posterior, mediodorsal, and reticular nuclei. In the neocortex, sensorimotor regions contain the most labeled neurons, but we find higher densities in associative areas, including orbital, anterior cingulate, prelimbic, and infralimbic cortex. Patterns of ascending expression correlate with c-Fos expression after optogenetic inhibition of Purkinje cells. Our results reveal homologous networks linking single areas of the cerebellar cortex to diverse forebrain targets. We conclude that shared areas of the cerebellum are positioned to provide sensory-motor information to regions implicated in both movement and nonmotor function.

Social memory deficit gated by dysregulation of the cerebellar vermis

“…Beside the vTH (ventrolateral and ventromedial thalamus), neurons in the centrolateral, parafascicular, mediodorsal, and ventral posteromedial thalamus, were strongly labeled (Fig. 6c, right), in line with recent anatomical studies 67,68 . Moreover, we observed neurons expressing tdTomato sparsely distributed in the dorsomedial and lateral hypothalamus.…”

“…The engagement of hippocampus and amygdala in the cerebellummediated SRM (Fig. 5) is likely through their intense crosstalk with other brain regions, such as the cerebral cortex 72,73 , that are connected to the DCN 67,68 . In fact, we observed a great number of labeled axons in the somatosensory cortex (S1 and S2), somatomotor cortex (M1) and PtA as well as moderate labeling in the Ect, mPFC (Acg, PL and IL) and ACC (Fig.…”

Mechanisms of Human Motor Learning Do Not Function Independently

“…The posterior lobules of the cerebellum are also reciprocally connected with prefrontal cognitive regions of the cerebral cortex, which are hypothesized to support the explicit learning process (Ramnani, 2006 ; Strick et al, 2009 ). The nature of the information sent through these pathways is unclear, but there is recent evidence to suggest homologous function across cerebellar projections (Pisano et al, 2021 ). However, the cerebellum contributes to a diverse set of behaviors, both motor and non-motor (Diedrichsen et al, 2019 ; King et al, 2019 ; Sereno et al, 2020 ).…”

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

“…In these experiments, Cre- or flippase-dependent molecular expression was usually triggered by AAV injection into the intermediate region or by usage of reporter mice. Moreover, polysynaptic connections from the cerebellum were analyzed using the retrograde and anterograde transneuronal viral tracers, rabies virus (RV) and herpes simplex virus strain H129, respectively, which enabled dissection of the complex connections from the cerebellum to the hippocampus or the neocortex ( Watson et al, 2019 ; Pisano et al, 2021 ).…”

“…The most direct measurement method of functional connections is electrophysiological recording from target regions during electrical, optogenetic, or chemogenetic manipulation of cerebellar activity ( Krook-Magnuson et al, 2014 ; Proville et al, 2014 ; Bambico et al, 2018 ; Gao et al, 2018 ; Carta et al, 2019 ; Chabrol et al, 2019 ; Frontera et al, 2020 ; Kelly et al, 2020 ; Zeidler et al, 2020 ; Dacre et al, 2021 ). The immunohistochemical analysis of activity-dependent molecules in target regions can be also used to detect activity changes in these regions after cerebellar manipulation ( Xiao et al, 2018 ; Zeidler et al, 2020 ; Pisano et al, 2021 ). Alterations of molecular expression patterns specifically in the cerebellum may disrupt the functional integrity of the cerebellum, and in turn result in activity changes in other brain regions ( Kelly et al, 2020 ; Rudolph et al, 2020 ; Han et al, 2021 ).…”