The anterior retrosplenial cortex encodes event-related information and the posterior retrosplenial cortex encodes context-related information during memory formation

Abstract

The retrosplenial cortex (RSC) is extensively interconnected with the dorsal hippocampus and has several important roles in learning and memory. Recent work has demonstrated that certain types of context-dependent learning are selectively impaired when the posterior, but not the anterior, region of the RSC is damaged, suggesting that the role of the RSC in memory formation may not be uniform along its rostro-caudal axis. The current experiments tested the idea that the anterior and posterior portions of the rat RSC contribute to different aspects of memory formation. We first confirmed that brief optogenetic inhibition of either the anterior or posterior RSC resulted in decreased local cellular activity as indexed by immediate early gene zif268 expression and that this decrease was restricted to the target region within RSC. We then found that silencing the anterior or posterior RSC during trace fear training trials had different effects on memory: While inhibiting neural activity in the anterior RSC had a selective impact on behavior evoked by the auditory CS, inhibition of the posterior RSC selectively impaired memory for the context in which training was conducted. These results contribute to a growing literature that supports functionally distinct roles in learning and memory for subregions of the RSC.

Fig. 1. Optogenetic inhibition results in a selective decrease in zif268 expression.

A A sagittal view highlighting the RSC along the anterior/posterior axis. B Percent zif268 expression (expressed as a proportion of total DAPI staining; mean and SEM) across the retrosplenial cortex in animals that had their aRSC inhibited or pRSC inhibited. Asterisks indicate a significant difference from the no light control group (p < 0.05). Vertical lines represent target virus infusion sites along the A/P axis.

Fig. 2. Behavioral results following optogenetic inhibition of the aRSC during TFC (Mean/SEM).

A–D Inhibition of the aRSC during the CS–UCS pairings. E–H aRSC inhibition during ITI of training. Design schematic depicted directly above figures. Green overlay in schematic indicates temporal placement of optogenetic inhibition. No group differences were demonstrated during training. UCS deliveries are marked by dashed lines (A, E). When inhibition of the aRSC occurred in the CS of acquisition but not the ITI, ArchT animals froze less during the CS during the CS test (B, F). No differences were seen when tested in the acquisition context (C, G), indicating that inhibition of the aRSC during acquisition selectively impacts CS freezing. D, H Representative images of virus expression along the sagittal plane (×4 magnification). Asterisks indicate p < 0.05.

Fig. 3. Behavioral results following optogenetic inhibition of the pRSC during TFC (Mean/SEM).

A–D aRSC inhibition during CS–UCS pairings. E–H Inhibition during ITI of training. Experimental design schematic depicted directly above figures. Green overlay in schematic indicates temporal placement of optogenetic inhibition. UCS deliveries are marked by dashed lines (A, E). No group differences were demonstrated during training (A, E) or during the CS test (B, F). Animals froze less to the acquisition context when their pRSC was inhibited during the training CS (C) but not when it was inhibited during the training ITI (G). Thus, pRSC inhibition during acquisition selectively impacts context freezing. D, H Representative images of virus expression along the sagittal plane (×4 magnification). See text for more details. Asterisks indicate p < 0.05.

Fig. 4. The main results from Figs. 2 and 3 were reanalyzed to express each animal’s responding as a percentage of the control animals responding in order to account for any between-experiment variability.

This analysis confirmed the results suggested by the raw data presented in Figs. 2 and 3. Inhibition of the aRSC during training trials reduced later freezing to the CS while leaving freezing to the context unaffected (A), but inhibition during the ITI had no impact (B). When the pRSC was inhibited during training trials (C), later freezing to the CS was not impacted but freezing to the training context was reduced. Inhibition of activity during the ITI did not impact later performance did not impact freezing to either the CS or the Context (D).