Cognitive and social capacities require postnatal experience, yet the pathways by which experience guides development are unknown. Here we show that the normal development of motor and nonmotor capacities requires cerebellar activity. Using chemogenetic perturbation of molecular layer interneurons to attenuate cerebellar output in mice, we found that activity of posterior regions in juvenile life modulates adult expression of eyeblink conditioning (paravermal lobule VI, crus I), reversal learning (lobule VI), persistive behavior and novelty-seeking (lobule VII), and social preference (crus I/II). Perturbation in adult life altered only a subset of phenotypes. Both adult and juvenile disruption left gait metrics largely unaffected. Contributions to phenotypes increased with the amount of lobule inactivated. Using an anterograde transsynaptic tracer, we found that posterior cerebellum made strong connections with prelimbic, orbitofrontal, and anterior cingulate cortex. These findings provide anatomical substrates for the clinical observation that cerebellar injury increases the risk of autism.

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.

16Cerebellar outputs take multisynaptic paths to reach higher brain areas, impeding tracing 17 efforts. Here we quantify pathways between cerebellum and contralateral 18 thalamic/corticostriatal structures using the anterograde transsynaptic tracer herpes 19 simplex virus type 1 (H129), the retrograde tracer pseudorabies virus (Bartha), adeno-20 associated virus, and a whole-brain pipeline for neuron-level analysis using light-sheet 21 microscopy. In ascending pathways, sensorimotor regions contained the most labeled 22 neurons, but higher densities were found in associative areas, including orbital, anterior 23 cingulate, prelimbic, and infralimbic cortex. Ascending paths passed through most 24 thalamic nuclei, especially ventral posteromedial and lateral posterior (sensorimotor), 25 mediodorsal (associative), and reticular (modulatory) nuclei. Retrograde tracing revealed 26 descending paths originating largely from somatomotor cortex. Patterns of ascending 27 influence correlated with anatomical pathway strengths, as measured by brainwide 28 mapping of c-Fos responses to optogenetic inhibition of Purkinje cells. Our results 29 reveal parallel functional networks linking cerebellum to forebrain and suggest that 30 cerebellum uses sensory-motor information to guide both movement and nonmotor 31 functions. 32 most mammalian brains 8 . The major descending corticocerebellar pathway passes through the 41 pons and the majority of returning ascending fibers pass through the thalamus 9,10 , comprising 42 two massive within-brain long-distance pathways 11 . Other polysynaptic pathways exist between 43 the cerebellum and neocortex, including a smaller ascending pathway through ventral tegmental 44 area that has attracted recent interest 12 . These descending and ascending pathways are 45 suggested to form closed loops 13 , giving each cerebellar region one or more specific neocortical 46 partners with which it exchanges information. 47This picture lacks critical information: the identity of those distant regions, which have 48 been difficult to map. Given the brain-wide nature of cerebello-cortical pathways, researchers 49 have used large-scale approaches to examine the functional significance of these pathways. 50Transcranial magnetic stimulation in humans demonstrated that the cerebellum influences 51 neocortical excitability 14 , including cognitive and affective circuits 15 . Functional MRI can attain 52 subcentimeter resolution, detect long-distance correlations 16 , and when coupled with cerebellar 53 stimulation, demonstrate causal relationships 17 . Functional imaging at cellular resolution in 54 nonhuman animals has been made possible by visualizing c-Fos, an immediate-early gene 55 product whose expression is regulated by neural activity. Although useful in demonstrating 56 communication with distant brain regions, these methods do not provide cellular-resolution 57 information about cerebello-cortical circuits. 58Pathways entering and exiting the cerebellum pass through synapses in the brainstem 59 and the cer...

Background: The ability to retain or improve seated balance function after spinal cord injury (SCI) may mean the difference between independence and requiring assistance for basic activities of daily living. Compared with assessments of standing and walking balance, seated balance assessments remain relatively underemphasized and under-utilized. Objective: To optimize tools for assessing seated balance deficits and recovery in SCI. Design: Cross-sectional observational study of different methods for assessing seated balance function. Setting: Veterans Affairs Center of Excellence for the Medical Consequences of Spinal Cord Injury. Participants: Seven able-bodied volunteers, seven participants with chronic motor-complete thoracic SCI. Interventions: A computerized pressure-plate apparatus designed for testing standing balance was adapted into a seated balance assessment system. Outcome measures: Seated section of Berg Balance Scale; modified functional reach test; and two posturography tests: limits of stability and clinical test of sensory integration on balance. Results: Seated posturography demonstrated improved correlation with neurological level of lesion compared to that of routinely applied subjective clinical tests. Conclusion: Seated posturography represents an appealing outcome measure that may be applied toward the measurement of functional changes in response to various rehabilitation interventions in individuals with paralysis.