Disrupting direct inputs from the dorsal subiculum to the granular retrosplenial cortex impairs spatial memory in the rat

Abstract

The dorsal subiculum is the primary source of hippocampal projections to the rat retrosplenial cortex. Although, both regions are implicated in spatial memory and navigation, the significance of their direct interconnections remains poorly understood. The present study selectively disrupted dorsal subiculum projections to retrosplenial cortex with inhibitory designer-receptors exclusively activated by designer drugs (iDREADDs), activated locally by clozapine. iDREADDs were injected in the dorsal subiculum in adult male rats (N=14), where they were transported anterogradely to granular retrosplenial cortex. In a separate control group, GFP expressing adeno-associated virus was injected into the dorsal subiculum (N=8). Both groups received behavioural sessions preceded either by intracerebral infusions of clozapine or saline within retrosplenial cortex. Behavioural testing involved reinforced T-maze alternation, with five test variations that differentially taxed intra-maze, extra-maze, and egocentric strategies. Disruption of the subiculum to retrosplenial projections impaired spatial working memory whenever the test variant created a conflict between cue-types, associated with a switch between different strategies. These findings suggest that the direct projections from the dorsal subiculum to the granular retrosplenial cortex help to maintain the flexible integration of different spatial cue-types.