Retrosplenial Cortical Contributions to Anterograde and Retrograde Memory in the Monkey

Abstract

Primate retrosplenial cortex (RSC) is important for memory but patient neuropathologies are diffuse so its key contributions to memory remain elusive. This study provides the first causal evidence that RSC in macaque monkeys is crucial for postoperative retention of preoperatively and postoperatively acquired memories. Preoperatively, monkeys learned 300 object-in-place scene discriminations across sessions. After RSC removal, one-trial postoperative retention tests revealed significant retrograde memory loss for these 300 discriminations relative to unoperated control monkeys. Less robust evidence was found for a deficit in anterograde memory (new postoperative learning) after RSC lesions as new learning to criterion measures failed to reveal any significant learning impairment. However, after achieving ≥90% learning criterion for the postoperatively presented novel 100 object-in-place scene discriminations, short-term retention (i.e., measured after 24 h delay) of this well-learnt set was impaired in the RSC monkeys relative to controls. A further experiment assessed rapid "within" session acquisition of novel object-in-place scene discriminations, again confirming that new learning per se was unimpaired by bilateral RSC removal. Primate RSC contributes critically to memory by supporting normal retention of information, even when this information does not involve an autobiographical component.

Keywords: amnesia; cingulate cortex; learning; lesion; macaque; retention.

Figure 1.

Three examples of object-in-place scene discrimination stimuli used in the 4 experiments in this study. The monkey responds to each “scene” by touching one of the 2 typographic foreground objects. One of the 2 foreground objects in each “scene” denoted by “S+” is arbitrarily designated as correct (reward). The “S−” indicates the locations of the unrewarded foreground objects in each “scene”. The locations and identities of the foreground objects are fixed within each scene, but vary across scenes.

Figure 2.

Schematic drawings of the intended bilateral retrosplenial cortex (RSC) ablations (first column) and ablations from the histology of the 5 monkeys (RSC1–5) with RSC damage (second–fifth columns) using the standard rhesus monkey brain (Saunders 2006). Numbers refer to the coronal sections from the atlas.

Figure 3.

Photomicrographs from the histology of the 5 monkeys with RSC ablations. The coronal sections shown correspond as closely as possible to the rostrocaudal coordinates (line 1, A + 5.6; line 2, A + 2.6; line 3, A + 1.6; line 4, A + 0.6) from (Kobayashi and Amaral 2000). Four monkeys (RSC1, RSC2, RSC3, RSC4) participated in the combined preoperative and postoperative one-trial retention tests of 300 object-in-place scene discriminations, relearning and postoperative learning across sessions of 100 novel object-in-place scene discriminations (Experiments 1–3) and one monkey (RSC5) participated in postoperative learning within-sessions of new object-in-place scene discriminations (Experiment 4).

Figure 4.

Preoperative and postoperative one-trial (per problem) retention test performance. Left, Total mean (+SEM) errors in memory retention for the unoperated controls (CON, n = 9) and bilateral retrosplenial cortex ablation (RSC, n = 4) monkeys during the preoperative (Pre, white bars) and postoperative (Post, black bars) one-trial retention tests summed over all 3 of the preoperatively learned sets (A–C). Right, The total mean (±SEM) errors per set made by unoperated control monkeys (CON, n = 9, circles; open circles = pre-op; black circles = post-op) and by bilateral retrosplenial cortex ablation monkeys (RSC, n = 4, triangles; open triangles = pre-op; black triangles = post-op) are shown for each of the 3 preoperatively learned sets (A–C) of 100 object-in-place scene discriminations each. Open symbols represent errors during the preoperative one-trial retention test; filled black symbols represent errors during the postoperative one-trial retention test.

Figure 5.

Preoperative and postoperative one-trial (per problem) retention test performance. (A) Total mean (+SEM) errors in memory retention during the preoperative (Pre, white bars) and postoperative (Post, black bars) one-trial retention tests for Set A; (B) for Set B; (C), for Set C for the unoperated controls monkeys (CON, n = 9), for bilateral retrosplenial cortex ablation monkeys (RSC, n = 4), for bilateral entorhinal cortex ablation monkeys (ERh, n = 3) and for bilateral neurotoxic lesions to magnocellular subdivision of the mediodorsal thalamus combined with bilateral fornix transection monkeys (MD + Fx, n = 3). The monkeys with ERh and MD + Fx lesions had been previously published (Mitchell et al. 2008).

Figure 6.

Postoperative relearning of preoperatively acquired problems. Total mean errors summed over all 3 of the preoperatively learned sets (A–C) for each group. Repetition cycles Pre and 1 are the preoperative and postoperative one-trail retention tests, respectively; Repetition cycles 2–4 are further repeats of the same postoperative one-trial retention test. Open symbols represent errors made during the preoperative one-trial retention test; filled black symbols represent errors made during the postoperative one-trial retention tests.

Figure 7.

Postoperative new learning of new problems: “Across session learning.” (A) Total mean (+SEM) errors in learning 100 novel object-in-place scene discriminations to ≥90% correct across 2 consecutive testing sessions (Experiment 3) during the novel postoperatively learned set (Set D, black bars). The final preoperatively learned set (Set C, white bars) is included for comparison. (B) Total mean (+SEM) retention errors measured 24 h after achieving ≥90% learning criterion in the first testing session for the postoperatively learnt novel 100 object-in-place scene discriminations made by unoperated control monkeys (CON, n = 9) and bilateral retrosplenial cortex ablation monkeys (RSC, n = 4).

Figure 8.

Postoperative new learning of new problems: “Rapid within” session learning. Mean percent error within-session learning curves (Experiment 4) for one monkey (RSC5) during learning of novel sets of 10 object-in-place scene discriminations with 8 repeats of 10 trials per session across the last 10 days of the within-session learning task, preoperatively (Pre-op), and postoperatively (Post-op) after bilateral retrosplenial cortex ablation (n = 1).