Loss of activity-dependent Arc gene expression in the retrosplenial cortex after hippocampal inactivation: Interaction in a higher-order memory circuit

Abstract

The rodent hippocampus is well known for its role in spatial navigation and memory, and recent evidence points to the retrosplenial cortex (RSC) as another element of a higher order spatial and mnemonic circuit. However, the functional interplay between hippocampus and RSC during spatial navigation remains poorly understood. To investigate this interaction, we examined cell activity in the RSC during spatial navigation in the water maze before and after acute hippocampal inactivation using expression of two immediate-early genes (IEGs), Arc and Homer 1a (H1a). Adult male rats were trained in a spatial water maze task for 4days. On day 5, the rats received two testing/training sessions separated by 20min. Eight minutes before the second session, different groups of rats received bilateral intrahippocampal infusion of tetrodotoxin (TTX), muscimol (MUS), or vehicle. Another group of rats (uni-TTX) received infusion of TTX in one hippocampus and vehicle in the other. Signals from Arc and H1a RNA probes correspond to the post- and pre-infusion sessions, respectively. Bilateral TTX and MUS impaired spatial memory, as expected, and decreased Arc expression in CA1 of hippocampus. Importantly, bilateral inactivation of hippocampus resulted in loss of behavior-induced Arc expression in RSC. Despite a lateralized effect in CA1, Arc expression was equivalently and bilaterally decreased in RSC of uni-TTX rats, consistent with a network level interaction between hippocampus and RSC. We conclude that the loss of hippocampal input alters activity of RSC neurons and compromises their ability to engage plastic processes dependent on IEG expression.