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

Abstract

SummaryWorking memory is a fundamental cognitive ability, allowing us to keep information in memory for the time needed to perform a given task. A complex neural circuit fulfills these functions, among which is the retrosplenial cortex (RSC). Functionally and anatomically connected to primary sensory cortices, namely visual areas, and to higher cognitive areas such as the cingulate, midcingulate, and subicular cortex, the 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 3 subsequent trials.