Optogenetic silencing of hippocampal inputs to the retrosplenial cortex causes a prolonged disruption of spatial working memory.

Working memory allows us to keep information in memory for the time needed to perform a given task. Such fundamental cognitive ability relies on a neural circuit, including the retrosplenial cortex (RSC), connected to several cortical areas, functionally and anatomically, namely primary visual areas, and higher cognitive areas such as the cingulate, midcingulate, and subicular cortices. RSC bears intimate anatomical and functional connections with the hippocampus and has been implicated in integrating and translating spatial-temporal contextual information between ego- and allocentric reference frames to compute predictions about goals in goal-directed behaviors. The relative contribution of the hippocampus and retrosplenial cortex in working memory-guided behaviors remains unclear due to the lack of studies reversibly interfering with synapses connecting the two regions during such behaviors. We here used eArch3.0, a hyperpolarizing proton pump, to silence hippocampal axon terminals in RSC while animals perform a standard delayed non-match to place task. We found that such manipulation impairs memory retrieval, significantly decreasing performance and hastening decision-making. Furthermore, we found that such impairment outlasts light activation of the opsin, its effects being noticed up to three subsequent trials.