Optogenetic stimulation of the basolateral amygdala-medial entorhinal cortex pathway after spatial training has sex-specific effects on downstream activity-regulated cytoskeletal-associated protein expression

Previous work from our laboratory suggests that projections from the basolateral amygdala (BLA) to the medial entorhinal cortex (mEC) are a critical pathway by which the BLA modulates the consolidation of spatial learning. Posttraining optogenetic stimulation of this pathway enhances retention of spatial memories. Evidence also indicates that intra-BLA administration of memory-enhancing drugs increases protein levels of activity-regulated cytoskeletal-associated protein (ARC) in the dorsal hippocampus (DH) and that blocking ARC in the DH impairs spatial memory consolidation. Yet, whether optical manipulations of the BLA-mEC pathway after spatial training also alter ARC in the DH is unknown. To address this question, male and female Sprague-Dawley rats received optogenetic stimulation of the BLA-mEC pathway immediately after spatial training using a Barnes maze and, 45 min later, were sacrificed for ARC analysis. Initial experiments found that spatial training increased ARC levels in the DH of rats above those observed in control rats and rats that underwent a cued-response version of the task. Optogenetic stimulation of the BLA-mEC pathway following spatial training, using parameters effective at enhancing spatial memory consolidation, enhanced ARC protein levels in the DH of male rats without affecting ARC levels in the dorsolateral striatum (DLS) or somatosensory cortex. In contrast, similar optical stimulation decreased ARC protein levels in the DLS of female rats without altering ARC in the DH or somatosensory cortex. Together, the present findings suggest a mechanism by which BLA-mEC stimulation enhances spatial memory consolidation in rats and reveals a possible sex-difference in this mechanism.