When is the rat retrosplenial cortex required for stimulus integration?

The rodent retrosplenial cortex is known to be vital for spatial cognition, but evidence has also pointed to a role in processing nonspatial information. It has been suggested that the retrosplenial cortex may serve as a site of integration of incoming sensory information. To examine this proposal, the current set of experiments assessed the impact of excitotoxic lesions in the retrosplenial cortex on two behavioral tasks that tax animals' ability to process multiple and overlapping environmental stimuli. In Experiment 1, rats with retrosplenial lesions acquired a negative patterning discrimination, a form of configural learning that can be solved only by learning the conjunction of cues. Subsequent transfer tests confirmed that both the lesion and control animals had solved the task by using configural representations. Furthermore, in Experiment 2, a 2nd cohort of retrosplenial lesion animals successfully acquired conditioned inhibition. Nevertheless, the same animals failed a subsequent summation test that assesses the ability to transfer what has been learned about one stimulus to another stimulus in the absence of reinforcement. Taken together, these results suggest that in the nonspatial domain, the retrosplenial cortex is not required for forming associations between multiple or overlapping environmental stimuli and, consequently, retrosplenial engagement in such processes is more selective than was previously envisaged. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Lesions of retrosplenial cortex spare immediate-early gene activity in related limbic regions in the rat.

The retrosplenial cortex forms part of a network of cortical and subcortical structures that have particular importance for spatial learning and navigation in rodents. This study examined how retrosplenial lesions affect activity in this network by visualising the expression of the immediate-early genes c-fos and zif268 after exposure to a novel location. Groups of rats with extensive cytotoxic lesions (areas 29 and 30) and rats with lesions largely confined to area 30 (dysgranular cortex) were compared with their respective control animals for levels of c-fos expression measured by immunohistochemistry. These cortical lesions had very limited effects on distal c-fos activity. Evidence of a restricted reduction in c-fos activity was seen in the septal dentate gyrus (superior blade) but not in other hippocampal and parahippocampal subareas, nor in the anterior cingulate and prelimbic cortices. Related studies examined zif268 activity in those cases with combined area 29 and 30 lesions. The only clear evidence for reduced zif268 activity following retrosplenial cell loss came from the septal CA3 area. The confined impact of retrosplenial tissue loss is notable as, by the same immediate-early gene measures, retrosplenial cortex is itself highly sensitive to damage in related limbic areas, showing a marked c-fos and zif268 hypoactivity across all of its subareas. This asymmetry in covert pathology may help to explain the apparent disparity between the severity of learning deficits after retrosplenial cortex lesions and after lesions in either the hippocampus or the anterior thalamic nuclei.

The rat retrosplenial cortex as a link for frontal functions: A lesion analysis.

Cohorts of rats with excitotoxic retrosplenial cortex lesions were tested on four behavioural tasks sensitive to dysfunctions in prelimbic cortex, anterior cingulate cortex, or both. In this way the study tested whether retrosplenial cortex has nonspatial functions that reflect its anatomical interactions with these frontal cortical areas. In Experiment 1, retrosplenial cortex lesions had no apparent effect on a set-shifting digging task that taxed intradimensional and extradimensional attention, as well as reversal learning. Likewise, retrosplenial cortex lesions did not impair a strategy shift task in an automated chamber, which involved switching from visual-based to response-based discriminations and, again, included a reversal (Experiment 2). Indeed, there was evidence that the retrosplenial lesions aided the initial switch to response-based selection. No lesion deficit was found on an automated cost-benefit task that pitted size of reward against effort to achieve that reward (Experiment 3). Finally, while retrosplenial cortex lesions affected matching-to-place task in a T-maze, the profile of deficits differed from that associated with prelimbic cortex damage (Experiment 4). When the task was switched to a nonmatching design, retrosplenial cortex lesions had no apparent effect on performance. The results from the four experiments show that many frontal tasks do not require the retrosplenial cortex, highlighting the specificity of their functional interactions. The results show how retrosplenial cortex lesions spare those learning tasks in which there is no mismatch between the internal and external representations used to guide behavioural choice. In addition, these experiments further highlight the importance of the retrosplenial cortex in solving tasks with a spatial component.

Dysgranular retrosplenial cortex lesions in rats disrupt cross-modal object recognition.

The retrosplenial cortex supports navigation, with one role thought to be the integration of different spatial cue types. This hypothesis was extended by examining the integration of nonspatial cues. Rats with lesions in either the dysgranular subregion of retrosplenial cortex (area 30) or lesions in both the granular and dysgranular subregions (areas 29 and 30) were tested on cross-modal object recognition (Experiment 1). In these tests, rats used different sensory modalities when exploring and subsequently recognizing the same test objects. The objects were first presented either in the dark, i.e., giving tactile and olfactory cues, or in the light behind a clear Perspex barrier, i.e., giving visual cues. Animals were then tested with either constant combinations of sample and test conditions (light to light, dark to dark), or changed "cross-modal" combinations (light to dark, dark to light). In Experiment 2, visual object recognition was tested without Perspex barriers, but using objects that could not be distinguished in the dark. The dysgranular retrosplenial cortex lesions selectively impaired cross-modal recognition when cue conditions switched from dark to light between initial sampling and subsequent object recognition, but no impairment was seen when the cue conditions remained constant, whether dark or light. The combined (areas 29 and 30) lesioned rats also failed the dark to light cross-modal problem but this impairment was less selective. The present findings suggest a role for the dysgranular retrosplenial cortex in mediating the integration of information across multiple cue types, a role that potentially applies to both spatial and nonspatial domains.

A novel role for the rat retrosplenial cortex in cognitive control.

By virtue of its frontal and hippocampal connections, the retrosplenial cortex is uniquely placed to support cognition. Here, we tested whether the retrosplenial cortex is required for frontal tasks analogous to the Stroop Test, i.e., for the ability to select between conflicting responses and inhibit responding to task-irrelevant cues. Rats first acquired two instrumental conditional discriminations, one auditory and one visual, set in two distinct contexts. As a result, rats were rewarded for pressing either the right or left lever when a particular auditory or visual signal was present. In extinction, rats received compound stimuli that either comprised the auditory and visual elements that signaled the same lever response (congruent) or signaled different lever responses (incongruent) during training. On conflict (incongruent) trials, lever selection by sham-operated animals followed the stimulus element that had previously been trained in that same test context, whereas animals with retrosplenial cortex lesions failed to disambiguate the conflicting response cues. Subsequent experiments demonstrated that this abnormality on conflict trials was not due to a failure in distinguishing the contexts. Rather, these data reveal the selective involvement of the rat retrosplenial cortex in response conflict, and so extend the frontal system underlying cognitive control.

Deletion of the GluA1 AMPA receptor subunit impairs recency-dependent object recognition memory.

Deletion of the GluA1 AMPA receptor subunit impairs short-term spatial recognition memory. It has been suggested that short-term recognition depends upon memory caused by the recent presentation of a stimulus that is independent of contextual-retrieval processes. The aim of the present set of experiments was to test whether the role of GluA1 extends to nonspatial recognition memory. Wild-type and GluA1 knockout mice were tested on the standard object recognition task and a context-independent recognition task that required recency-dependent memory. In a first set of experiments it was found that GluA1 deletion failed to impair performance on either of the object recognition or recency-dependent tasks. However, GluA1 knockout mice displayed increased levels of exploration of the objects in both the sample and test phases compared to controls. In contrast, when the time that GluA1 knockout mice spent exploring the objects was yoked to control mice during the sample phase, it was found that GluA1 deletion now impaired performance on both the object recognition and the recency-dependent tasks. GluA1 deletion failed to impair performance on a context-dependent recognition task regardless of whether object exposure in knockout mice was yoked to controls or not. These results demonstrate that GluA1 is necessary for nonspatial as well as spatial recognition memory and plays an important role in recency-dependent memory processes.