Context value updating and multidimensional neuronal encoding in the retrosplenial cortex

The retrosplenial cortex (RSC) has diverse functional inputs and is engaged by various sensory, spatial, and associative learning tasks. We examine how multiple functional aspects are integrated on the single-cell level in the RSC and how the encoding of task-related parameters changes across learning. Using a visuospatial context discrimination paradigm and two-photon calcium imaging in behaving mice, a large proportion of dysgranular RSC neurons was found to encode multiple task-related dimensions while forming context-value associations across learning. During reversal learning requiring increased cognitive flexibility, we revealed an increased proportion of multidimensional encoding neurons that showed higher decoding accuracy for behaviorally relevant context-value associations. Chemogenetic inactivation of RSC led to decreased behavioral context discrimination during learning phases in which context-value associations were formed, while recall of previously formed associations remained intact. RSC inactivation resulted in a persistent positive behavioral bias in valuing contexts, indicating a role for the RSC in context-value updating.

Topographically organized representation of space and context in the medial prefrontal cortex

Spatial tuning of pyramidal cells has been observed in diverse neocortical regions, but a systematic characterization of the properties of spatially tuned neurons across cortical layers and regions is lacking. Using mice navigating through virtual environments, we find topographical organizational principles for the representation of spatial features in the medial prefrontal cortex. We show that spatial tuning emerges across layers with a dorso-ventral gradient in the depth of spatial tuning, which resides in superficial layers. Moreover, the prefrontal cortex shows hemispheric lateralization of spatial tuning such that neurons located in the left hemisphere display more pronounced spatial tuning. During exploration of a novel compared to a familiar context, a different picture emerges. Context discrimination and familiarity detection is higher in superficial compared to deep layers. However, neurons of the right medial prefrontal cortex discriminate more efficiently between contexts than cells in the left hemisphere. Jointly, these results reveal a complex topographic organization of spatial representation and suggest a division of labor among prefrontal layers and subregions in the encoding of spatial position in the current environment and context discrimination.