Disynaptic cerebrocerebellar pathways originating from multiple functionally distinct cortical areas.

The cerebral cortex and cerebellum both play important roles in sensorimotor processing, however, precise connections between these major brain structures remain elusive. Using anterograde mono-trans-synaptic tracing, we elucidate cerebrocerebellar pathways originating from primary motor, sensory, and association cortex. We confirm a highly organized topography of corticopontine projections in mice; however, we found no corticopontine projections originating from primary auditory cortex and detail several potential extra-pontine cerebrocerebellar pathways. The cerebellar hemispheres were the major target of resulting disynaptic mossy fiber terminals, but we also found at least sparse cerebrocerebellar projections to every lobule of the cerebellum. Notably, projections originating from association cortex resulted in less laterality than primary sensory/motor cortices. Within molecularly defined cerebellar modules we found spatial overlap of mossy fiber terminals, originating from functionally distinct cortical areas, within crus I, paraflocculus, and vermal regions IV/V and VI - highlighting these regions as potential hubs for multimodal cortical influence.

Action and learning shape the activity of neuronal circuits in the visual cortex.

Nonsensory variables strongly influence neuronal activity in the adult mouse primary visual cortex. Neuronal responses to visual stimuli are modulated by behavioural state, such as arousal and motor activity, and are shaped by experience. This dynamic process leads to neural representations in the visual cortex that reflect stimulus familiarity, expectations of reward and object location, and mismatch between self-motion and visual-flow. The recent development of genetic tools and recording techniques in awake behaving mice has enabled the investigation of the circuit mechanisms underlying state-dependent and experience-dependent neuronal representations in primary visual cortex. These neuronal circuits involve neuromodulatory, top-down cortico-cortical and thalamocortical pathways. The functions of nonsensory signals at this early stage of visual information processing are now beginning to be unravelled.

Behavioral-state modulation of inhibition is context-dependent and cell type specific in mouse visual cortex.

Cortical responses to sensory stimuli are modulated by behavioral state. In the primary visual cortex (V1), visual responses of pyramidal neurons increase during locomotion. This response gain was suggested to be mediated through inhibitory neurons, resulting in the disinhibition of pyramidal neurons. Using in vivo two-photon calcium imaging in layers 2/3 and 4 in mouse V1, we reveal that locomotion increases the activity of vasoactive intestinal peptide (VIP), somatostatin (SST) and parvalbumin (PV)-positive interneurons during visual stimulation, challenging the disinhibition model. In darkness, while most VIP and PV neurons remained locomotion responsive, SST and excitatory neurons were largely non-responsive. Context-dependent locomotion responses were found in each cell type, with the highest proportion among SST neurons. These findings establish that modulation of neuronal activity by locomotion is context-dependent and contest the generality of a disinhibitory circuit for gain control of sensory responses by behavioral state.