Specific anterior-posterior brain-wide input patterns support specialized visuospatial processing in the mouse retrosplenial cortex

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Abstract

The retrosplenial cortex (RSC) is a key integrative hub involved in spatial orientation, navigation, and diverse cognitive and mnemonic processes. In rodents, RSC neurons carry rich sensory and navigational signals and are interconnected with sensory, motor, thalamic, and hippocampal circuits, supporting multimodal integration. However, the cellular circuit mechanisms that underlie this integration remain poorly understood. Here, we combined two-photon calcium imaging in navigating mice with brain-wide retrograde tracing to investigate how visual and positional signals are encoded and distributed across the RSC, with functional data covering both the medial-to-lateral and anterior-to-posterior dimensions of the RSC. We found that anterior and posterior RSC neurons exhibit distinct encoding properties and afferent connectivity. While anterior RSC neurons preferentially encode high-speed visual motion and display sharp, reliable position tuning, posterior RSC neurons are more responsive to low-speed stimuli and exhibit broader, weaker position-related activity. These functional specializations are paralleled by distinct long-range input patterns: anterior RSC receives dense projections from motor, parietal, and hippocampal-related areas, regions associated with strong position-related signals, whereas posterior RSC is more strongly innervated by visual cortices. Together, our results reveal a topographic organization of visual and navigational signals in the RSC, with anatomically distinct subregions potentially supporting different roles in visuospatial integration during navigation.

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