The retrosplenial cortex and object recency memory in the rat

Abstract

It has been proposed that the retrosplenial cortex forms part of a 'where/when' information network. The present study focussed on the related issue of whether retrosplenial cortex also contributes to 'what/when' information, by examining object recency memory. In Experiment 1, rats with retrosplenial lesions were found to be impaired at distinguishing the temporal order of objects presented in a continuous series ('Within-Block' condition). The same lesioned rats could, however, distinguish between objects that had been previously presented in one of two discrete blocks ('Between-Block' condition). Experiment 2 used intact rats to map the expression of the immediate-early gene c-fos in retrosplenial cortex following performance of a between-block, recency discrimination. Recency performance correlated positively with levels of c-fos expression in both granular and dysgranular retrosplenial cortex (areas 29 and 30). Expression of c-fos in the granular retrosplenial cortex also correlated with prelimbic cortex and ventral subiculum c-fos activity, the latter also correlating with recency memory performance. The combined findings from both experiments reveal an involvement of the retrosplenial cortex in temporal order memory, which includes both between-block and within-block problems. The current findings also suggest that the rat retrosplenial cortex comprises one of a group of closely interlinked regions that enable recency memory, including the hippocampal formation, medial diencephalon and medial frontal cortex. In view of the well-established importance of the retrosplenial cortex for spatial learning, the findings support the notion that, with its frontal and hippocampal connections, retrosplenial cortex has a key role for both what/when and where/when information.

Keywords: c-fos; hippocampus; recognition memory; subiculum; temporal discrimination.

Figure 1

The shape and dimensions (cm) of the bow‐tie maze used in Experiments 1 and 2. The circles in the plan (left) depict the locations of the food wells, which is where objects were placed. [Colour figure can be viewed at wileyonlinelibrary.com].

Figure 2

Schematic diagram showing the sequence of object presentation in Experiments 1a, 1b and 2. Different objects are represented by different letters and by changes in case (upper or lower). To represent the first presentation of an object in the Sample Phase (i.e. when novel), the letter is in bold. Bold typeface in the Test Phase reflects that object in the trial that was first encountered longer ago in time. The Table shows the order of object presentation across the different Phases of the Between‐Block (Experiment 1a) and Within‐Block (Experiment 1b) recency procedures. The Within‐Block condition (Experiment 1b) did not involve a separate Sample Phase prior to the Test Phase as these phases were integrated into a single, continuous session. In the Test Phases in all four conditions (Experiments 1, 2) each trial involved two different, familiar objects from different times in the past.

Figure 3

The regions of interest within the retrosplenial cortex (A) and related areas (B). Examples of sections stained for Fos protein in retrosplenial cortex (C) and related areas (D). Abbreviations: ATN, anterior thalamic nuclei, consisting of the AD (anterodorsal), AM (anteromedial) and (AV) anteroventral nuclei; PL, prelimbic cortex; Sub, subiculum (d, dorsal, v, ventral). The other labels refer to different subregions within retrosplenial cortex (Van Groen & Wyss, 2003). The numbers refer to distance from bregma (Paxinos & Watson, 2005). Scale bar = 200 μm. [Colour figure can be viewed at wileyonlinelibrary.com].

Figure 4

Location and extent of the retrosplenial cortex lesions (Experiments 1 a and b). A. The largest (pale grey) and smallest (dark grey) cortical lesions on a series of coronal sections. B. Photomicrographs from a representative lesion (top row) and a surgical sham case (bottom row). (See Fig. 3 for the divisions within retrosplenial cortex). Scale bars represent 200 μm. The numbers refer to the approximate distance in mm of each section caudal to bregma (Paxinos & Watson, 2005). [Colour figure can be viewed at wileyonlinelibrary.com].

Figure 5

Experiment 1a, Between‐Block Recency. (A) The final D2 scores from Sample Phase 1 and 2 (recognition), as well as the Recency Test Phase in both groups. (B) Total exploration time during the two Sample Phases and the Test Phase in the retrosplenial cortex lesion (RSC) and Sham groups. The central line on each box shows the median value. The box extends from the first to the third quartile. The upper and lower whiskers extend 1.5× interquartile range. Note that data points were ‘jittered’ on the x‐axis, by adding random noise to the values of the categorical variable, in order to better visualise overlapping data points.

Figure 6

Experiment 1b, Within‐Block Recency. (A) Total exploration time per trial during the Sample and Test Phases in the retrosplenial (RSC) lesion and Sham groups. (B) The final D2 scores from the Test Phase in both groups (B). The central line on each box shows the median value. The box extends from the first to the third quartile. The upper and lower whiskers extend 1.5× interquartile range. Note that data points were ‘jittered’ on the x‐axis (see Fig. 5).

Figure 7

Experiment 2, c‐fos expression associated with recency memory. (A) Total times spent exploring objects during the Test Phase of the Recency Test and the Recency Control conditions. (B) Final D2 scores for the Recency Test and the Recency Control. The central line on each box shows the median value. The box extends from the first to the third quartile. The upper and lower whiskers extend 1.5× interquartile range. Note that data points were ‘jittered’ on the x‐axis (see Fig. 5).

Figure 8

Experiment 2, c‐fos expression associated with recency memory. Comparison of the Fos‐positive cell counts in each of the major retrosplenial subareas for the Recency Test and Recency Control groups. Error bars show ± SEM. Abbreviations: DysG.Deep: Dysgranular cortex, deep layers; DysG.Sup: Dysgranular cortex, superficial layers; G.Deep, Granular cortex, deep layers; G.Sup: Granular cortex, superficial layers. The central line on each box shows the median value. The box extends from the first to the third quartile. The upper and lower whiskers extend 1.5× interquartile range. Note that data points were ‘jittered’ on the x‐axis (see Fig. 5).

Figure 9

Experiment 2, c‐fos expression associated with recency memory. Scatter plots of the Fos‐positive cell counts and the individual D2 recency memory scores for each of the nine animals in the (A) Recency Test group and (B) Recency Control group. Abbreviations: DysG.Deep: Dysgranular cortex, deep layers; DysG.Sup: Dysgranular cortex, superficial layers; G.Deep, Granular cortex, deep layers; G.Sup: Granular cortex, superficial layers.