Extensive cytotoxic lesions of the rat retrosplenial cortex reveal consistent deficits on tasks that tax allocentric spatial memory.

Despite the connections of the retrosplenial cortex strongly suggesting a role in spatial memory, the lesion data to date have been equivocal. Whether subjects are impaired after retrosplenial lesions seems to depend on whether the lesions were aspirative or excitotoxic, with the latter failing to produce an impairment. A shortcoming of previous excitotoxic lesion studies is that they spared the most caudal part of the retrosplenial cortex. The present study thus used rats with extensive neurotoxic lesions of the retrosplenial cortex that encompassed the entire rostrocaudal extent of this region. These rats were consistently impaired on several tests that tax allocentric memory. In contrast, they were unimpaired on an egocentric discrimination task. Although the lesions did not appear to affect object recognition, clear deficits were found for an object-in-place discrimination. The present study not only demonstrates a role for the retrosplenial cortex in allocentric spatial memory, but also explains why previous excitotoxic lesions have failed to detect any deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective dysgranular retrosplenial cortex lesions in rats disrupt allocentric performance of the radial-arm maze task.

The present study provides the 1st report on the effects of selective lesions of the dysgranular portion of the retrosplenial cortex in rats. Excitotoxic lesions of the dysgranular area were sufficient to impair behavior in the radial-arm maze by biasing the strategy used to solve the task. In particular, rats with dysgranular retrosplenial lesions were less reliant on distal visual cues to control performance of a working memory task in the radial-arm maze. Instead, they were more reliant on using a motor turning strategy to solve the task. This change in strategy is consistent with anatomical data showing that the dysgranular region is the primary recipient of visual inputs to the rat retrosplenial cortex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of cytotoxic perirhinal cortex lesions on spatial learning by rats: A comparison of the dark Agouti and Sprague-Dawley strains.

The effects of perirhinal cortex lesions in rats on spatial memory might depend on the choice of strain. The present study, therefore, compared perirhinal lesions in Sprague-Dawley rats (associated with deficits) with Dark Agouti rats (associated with null effects). Tests of reference memory and working memory in the water maze failed to provide evidence that perirhinal lesions disrupt overall levels of performance (irrespective of strain) or that these lesions have differential effects on the rates of spatial learning in these 2 strains. Strain differences were, however, found, as the Dark Agouti strain was often superior. Furthermore, the perirhinal lesions did have differential effects in the 2 strains, but these did not appear to relate directly to changes in spatial learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the perirhinal cortex do not impair integration of visual and geometric information in rats.

Rats with lesions of the perirhinal cortex and a control group were required to find a platform in 1 corner of a white rectangle and in the reflection of this corner in a black rectangle. Test trials revealed that these groups were able to integrate information regarding the shape of the pool and the color of its walls (black or white) to identify the correct location of the platform. A clear effect of the perirhinal cortex lesions was, however, revealed using an object recognition task that involved the spontaneous exploration of novel objects. The results challenge the view that the perirhinal cortex enables rats to solve discriminations involving feature ambiguity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurotoxic lesions of retrosplenial cortex disrupt signaled and unsignaled contextual fear conditioning.

The majority of research regarding contextual learning and memory has focused on the contributions of the hippocampus and related medial temporal lobe structures. However, little is known about other possible cortical contributions to these processes. Our laboratory recently demonstrated that electrolytic lesions of the retrosplenial cortex (RSP), a posterior region of cingulate cortex, impaired contextual but not cue-specific fear conditioning. The present experiments further examined the role of RSP in contextual fear memory using fiber-sparing neurotoxic lesions and both signaled and unsignaled fear conditioning paradigms. Despite comparable acquisition of the conditioned fear response, rats with neurotoxic lesions of RSP exhibited impaired contextual memory relative to control animals in both the signaled and unsignaled paradigms. These results further suggest an important role for RSP in contextual learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of NMDA lesions centered on the postrhinal cortex on spatial memory tasks in the rat.

Rats with bilateral N-methyl-D-aspartate lesions centered on the postrhinal cortex (POR) and sham lesions were tested in a series of spatial memory tasks. The POR-lesioned rats were significantly impaired compared with sham rats in the reference memory version of both the water maze and radial arm maze tasks and in the standard radial arm maze working memory task. The POR-lesioned rats displayed a delay-independent impairment in the working memory versions of the water maze and in a delayed nonmatching-to-place (DNMP) version of the radial arm maze task. The POR-lesioned rats were also impaired in a DNMP procedure conducted in the T-maze. These findings indicate that the POR has a delay-independent role in the processing of spatial information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the rat perirhinal cortex spare the acquisition of a complex configural visual discrimination yet impair object recognition.

Rats with perirhinal cortex lesions were sequentially trained in a rectangular water tank on a series of 3 visual discriminations, each between mirror-imaged stimuli. When these same discriminations were tested concurrently, the rats were forced to use a configural strategy to solve the problems effectively. There was no evidence that lesions of the perirhinal cortex disrupted the ability to learn the concurrent configural discrimination task, which required the rats to learn the precise combination of stimulus identity with stimulus placement (“structural” learning). The same rats with perirhinal cortex lesions were also unimpaired on a test of spatial working memory (reinforced T maze alternation), although they were markedly impaired on a new test of spontaneous object recognition. For the recognition test, rats received multiple trials within a single session in which on every trial, they were allowed to explore 2 objects, 1 familiar, the other novel. On the basis of their differential exploration times, rats with perirhinal cortex lesions showed very poor discrimination of the novel objects, thereby confirming the effectiveness of the surgery. The discovery that bilateral lesions of the perirhinal cortex can leave configural (structural) learning seemingly unaffected points to a need to refine those models of perirhinal cortex function that emphasize its role in representing conjunctions of stimulus features. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Two forms of spatial memory: A double dissociation between the parietal cortex and the hippocampus in the rat.

Two variants of a continuous recognition training procedure were designed in order to query 2 forms of spatial memory. A continuous reinforcement condition (reflecting perceptual memory) and a differential reinforcement condition (reflecting episodic-like memory) were used to test rats on a 12-arm radial maze. After total hippocampal lesions, rats demonstrated intact performance on the continuous reinforcement condition, but impaired performance on the differential reinforcement condition. After parietal lesions, rats demonstrated the reverse pattern of performance: impaired performance on the continuous reinforcement condition and intact performance on the differential reinforcement condition. Thus, a double dissociation appears to exist between parietal cortex and hippocampus for the continuous reinforcement condition (reflecting perceptual memory) versus the differential reinforcement condition (reflecting episodic memory) for spatial location information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impairment of radial maze delayed nonmatching after lesions of anterior thalamus and parahippocampal cortex.

This study compared the effects of lesions damaging hippocampus-related pathways in anterior thalamus (AT) and parahippocampal (PH) cortex on allocentric spatial memory. Rats were trained to perform radial maze delayed nonmatching (DNM) with random selection of arms to prevent egocentric solutions. After experimental treatment (control, excitotoxic AT, radiofrequency PH, or combined AT-PH lesions), rats were retrained for 30 sessions from 2 to 8 weeks after surgery. Results showed comparable impairments for AT and PH lesions that added without interaction in the combined AT-PH group. During chronic recovery, the AT-PH group exhibited delay-dependent deficits comparable to previous results for hippocampal lesions. Thus, AT and PH lesions appear to have separate effects that together disrupt hippocampus-dependent spatial memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Suppression to visual, auditory, and gustatory stimuli habituates normally in rats with excitotoxic lesions of the perirhinal cortex.

In 3 habituation experiments, rats with excitotoxic lesions of the perirhinal cortex were found to be indistinguishable from control rats. Two of the habituation experiments examined the habituation of suppression of responding on an appetitive, instrumental baseline. One of those experiments used stimuli selected from the visual modality (lights), the other used auditory stimuli. The third experiment examined habituation of suppression of novel-flavored water consumption. In contrast to the null results on the habituation experiments, the perirhinal lesions disrupted transfer performance on a configural, visual discrimination, indicating the behavioral effectiveness of the lesions. Implications for comparator theories of habituation are considered, and it is concluded that others’ demonstrations of the sensitivity of object recognition to perirhinal cortex damage is not the result of standard habituation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory learning and memory impairments following lesions to the hippocampus and perirhinal-entorhinal cortex.

The role of the hippocampus and perirhinal-entorhinal cortex was examined in an olfactory discrimination paradigm. Small neurotoxic lesions of the hippocampus (21% tissue damage) yielded relatively unimpaired olfactory retention across brief (30 s), intermediate (approximately 5 min), and 24-hr delays, whereas impairments were noted at 5-day retention intervals. Larger hippocampal lesions (63% tissue damage) spared memory at intermediate delays, with no impact at 8-day retention intervals. Aspiration lesions directed at the perirhinal-entorhinal cortex produced a variable performance pattern, with impairments noted at intermediate, 24-hr, and 5-day delays. Results suggest the hippocampus is not specifically involved in retaining olfactory information, with additional consideration given to the relationship between lesion size and memory impairment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Familiarity-based stimulus generalization of conditioned suppression in rats is dependent on the perirhinal cortex.

We report that bilateral, excitoxic lesions of the perirhinal cortex attenuate rats' familiarity-based stimulus generalization. After surgery, rats were preexposed either to 2 auditory stimuli (A and B) or to only 1 auditory stimulus (B). Following preexposure, all rats received pairings of A and a footshock before assessment of generalized responding (conditioned suppression) to B. Sham rats' generalization was greater when preexposure was to both A and B than when preexposure was to B only. That pattern was abolished in lesioned rats, though no general deficiency was found in other measures of auditory processing. Our findings suggest that the perirhinal cortex is required for rats to encode familiarity as part of stimulus representations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Finding your way in the dark: The retrosplenial cortex contributes to spatial memory and navigation without visual cues.

Path integration is presumed to rely on self-motion cues to identify locations in space and is subject to cumulative error. The authors tested the hypothesis that rats use memory to reduce such errors and that the retrosplenial cortex contributes to this process. Rats were trained for 1 week to hoard food in an arena after beginning a trial from a fixed starting location; probe trials were then conducted in which they began a trial from a novel place in light or darkness. After control injections, rats searched around the training location, showing normal spatial memory. Inactivation of the retrosplenial cortex disrupted this search preference. To assess accuracy during navigation, rats were then trained to perform multiple trials daily, with a fixed or a different starting location in light or darkness. Retrosplenial cortex inactivation impaired accuracy in darkness. The retrosplenial cortex may provide mnemonic information, which decreases errors when navigating in the dark. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual fear discrimination is impaired by damage to the postrhinal or perirhinal cortex.

Postrhinal (POR) or perirhinal (PER) cortex damage impairs acquisition and expression of contextual fear, but the nature of the impairment remains unclear. This study used a contextual fear discrimination paradigm that biased subjects toward using a configural, rather than an elemental, strategy to distinguish between 2 contexts, 1 of which was paired with a mild footshock. Control rats discriminated between 2 contexts when a combination of several cues could be used (Exp 1), but not when individual sensory cues were manipulated (Exp 2). Rats with POR or PER lesions could not discriminate between the shock and no-shock contexts when multiple cues differentiated the contexts (Exp 3). The results indicate that both the POR and PER have a role in configural learning of contextual fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective neurotoxic amygdala lesions in monkeys disrupt reactivity to food and object stimuli and have limited effects on memory.

Monkeys with bilateral neurotoxic amygdala lesions and normal monkeys were administered tests of emotional reactivity, recognition memory, and reward association memory. There were 3 main findings. First, monkeys with amygdala lesions performed differently than normal monkeys on initial administrations of the emotional reactivity tests and on retests that were given 21-23 months after surgery. Second, they performed like normal monkeys on tests of recognition memory. Third, they were initially impaired on a test of reward association memory, but they were not impaired on a retest that was given 16 months after surgery. These findings underscore the role of the amygdala in aspects of emotional reactivity and reward association memory, but not in recognition memory. In addition, at least some of the behavioral effects of amygdala damage can be long lasting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Performance on spatial working memory tasks after dorsal or ventral hippocampal lesions and adjacent damage to the subiculum.

Rats with excitotoxic lesions of the dorsal or ventral hippocampus and control rats were trained on 2 spatial working memory tasks: the standard version of the radial maze with 8 baited arms and the nonmatching-to-place procedure in the T maze. Dorsal lesions produced deficits in both tasks, whereas ventral lesions did not affect learning in either of them. A volumetric analysis of subicular damage showed that dorsal hippocampal lesions caused a deficit in the nonmatching-to-place only when accompanied by damage to the dorsal subiculum; on the other hand, lesions to the dorsal hippocampus impaired performance in the radial-arm maze regardless of the extent of subicular damage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociable Effects of Lesions to the Perirhinal Cortex and the Postrhinal Cortex on Memory for Context and Objects in Rats.

Memory for the context in which an object appeared was investigated with a version of the spontaneous object recognition paradigm. Sham-operated rats explore familiar objects appearing in incongruent but familiar contexts more than those appearing in congruent contexts, revealing memory for the context in which an object previously appeared. At short delays, perirhinal cortex-lesioned rats were unimpaired on memory for object in context, whereas fornix-lesioned rats showed only a mild impairment. In contrast, postrhinal lesions resulted in severe deficits. However, in a comparable noncontextual object task, postrhinal and fornix lesions had no effect, whereas perirhinal-lesioned rats were severely impaired. Comparison of these tasks and other published data may shed light on the nature of the contextual processing involved. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential roles of dorsal hippocampal subregions in spatial working memory with short versus intermediate delay.

In order to determine the role of subregions of the hippocampus in spatial working memory, this study combined selective neurotoxic lesions of the hippocampal subregions with a simple delayed nonmatching-to-place task on a radial maze in rats. Lesions of the dentate gyrus or the CA3, but not the CA1, subregion of the hippocampus induced a deficit in the acquisition of the task with short-term delays (i.e., 10 sec) and impaired performance of the task in a novel environment. All subregional lesions produced sustained impairment in performing the task with intermediate-term delays (i.e., 5 min) when rats were tested in a familiar environment. The results suggest a dynamic interaction among the dorsal hippocampal subregions in processing spatial working memory, with the time window (i.e., delay) of a task recognized as an essential controlling factor. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cooperation between memory systems: Acetylcholine release in the amygdala correlates positively with performance on a hippocampus-dependent task.

The present experiment examined the relationship between release of acetylcholine (ACh) in the amygdala and performance on a hippocampus-dependent spatial working memory task. Using in vivo microdialysis, the authors measured ACh release in rats during testing on a spontaneous alternation task. Amygdala ACh release was positively correlated with performance on the hippocampus-dependent task. These findings suggest that activation of the amygdala promotes processing in other neural systems important for learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Entorhinal cortex lesions disrupt the transition between the use of intra- and extramaze cues for navigation in the water maze.

[Correction Notice: An erratum for this article was reported in Vol 117(5) of Behavioral Neuroscience (see record 2007-16848-001). The definitions "Present = intramaze landmark present during Stage 2" and "Absent = intramaze landmark absent during Stage 2" appear incorrectly in the caption to Figure 3. These terms and definitions should appear in the caption to Figure 4.] This study with rats examined the effects of excitotoxic lesions to the entorhinal cortex (EC) and hippocampus (HPC) on using extramaze and intramaze cues to navigate to a hidden platform in a water maze. HPC lesions resulted in a disruption to the use of extramaze cues, but not intramaze cues, whereas EC lesions had no effect on the use of these cues when they were encountered for the fast time. However, prior navigation training in which 1 type of cue was relevant disrupted navigation with the other type in rats with EC lesions. Results show that the EC contributes to the processing of spatial information, but that this contribution is most apparent when there is a conflict between 2 sources of navigational cues in the water maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)