Perirhinal cortex lesions that impair object recognition memory spare landmark discriminations

Rats with lesions in the perirhinal cortex and their control group learnt to discriminate between mirror-imaged visual landmarks to find a submerged platform in a watermaze. Rats initially learnt this discrimination passively, in that they were repeatedly placed on the platform in one corner of a square watermaze with walls of different appearance, prior to swimming to that same location for the first time in a subsequent probe trial. Perirhinal cortex lesions spared this passively learnt ability, despite the common visual elements shared by the guiding landmarks. These results challenge models of perirhinal function that emphasise its role in solving discriminations between stimuli with ambiguous or overlapping features, while underlining how this cortical region is often not required for spatial processes that involve the hippocampus

Why do lesions in the rodent anterior thalamic nuclei cause such severe spatial deficits?

Lesions of the rodent anterior thalamic nuclei cause severe deficits to multiple spatial learning tasks. Possible explanations for these effects are examined, with particular reference to T-maze alternation. Anterior thalamic lesions not only impair allocentric place learning but also disrupt other spatial processes, including direction learning, path integration, and relative length discriminations, as well as aspects of nonspatial learning, e.g., temporal discriminations. Working memory tasks, such as T-maze alternation, appear particularly sensitive as they combine an array of these spatial and nonspatial demands. This sensitivity partly reflects the different functions supported by individual anterior thalamic nuclei, though it is argued that anterior thalamic lesion effects also arise from covert pathology in sites distal to the thalamus, most critically in the retrosplenial cortex and hippocampus. This two-level account, involving both local and distal lesion effects, explains the range and severity of the spatial deficits following anterior thalamic lesions. These findings highlight how the anterior thalamic nuclei form a key component in a series of interdependent systems that support multiple spatial functions

Neurotoxic lesions of the dorsomedial thalamus impair the acquisition but not the performance of delayed matching to place by rats: a deficit in shifting response rules

This study examined the acquisition of a T-maze matching to place task by rats with neurotoxic lesions of the thalamic nucleus medialis dorsalis. This test of spatial working memory also entails learning a task rule that is contrary to the animals’ innate preference. The rats next performed the same matching task over different retention delays. Finally, they were trained on a reversal of the task rule, i.e., to nonmatch to place. Although the lesions produced a clear acquisition impairment on the matching task, there was no evidence of a loss of working memory. A series of control tasks found no appreciable effect on a conditioned cue preference task or on open field activity. The pattern of results shows that medialis dorsalis lesions lead to a selective increase in perseverative behavior that can retard task acquisition. This perseverative deficit closely resembles that observed after prefrontal damage in rats, strongly indicating dysfunction in a common system

Episodic memory, amnesia and the hippocampal - anterior thalamic axis

By utilizing new information from both clinical and experimental (lesion, electrophysiological, and gene-activation) studies with animals, the anatomy underlying anterograde amnesia has been reformulated. The distinction between temporal lobe and diencephalic amnesia is of limited value in that a common feature of anterograde amnesia is damage to part of an “extended hippocampal system” comprising the hippocampus, the fornix, the mamillary bodies, and the anterior thalamic nuclei. This view, which can be traced back to Delay and Brion (1969), differs from other recent models in placing critical importance on the efferents from the hippocampus via the fornix to the diencephalon. These are necessary for the encoding and, hence, the effective subsequent recall of episodic memory. An additional feature of this hippocampal–anterior thalamic axis is the presence of projections back from the diencephalon to the temporal cortex and hippocampus that also support episodic memory. In contrast, this hippocampal system is not required for tests of item recognition that primarily tax familiarity judgements. Familiarity judgements reflect an independent process that depends on a distinct system involving the perirhinal cortex of the temporal lobe and the medial dorsal nucleus of the thalamus. In the large majority of amnesic cases both the hippocampal–anterior thalamic and the perirhinal–medial dorsal thalamic systems are compromised, leading to severe deficits in both recall and recognition

Evidence of a spatial encoding deficit in rats with lesions of the mammillary bodies or mammillothalamic tract

The present study sought to identify the role of the mammillary bodies and their projections to the anterior thalamic nuclei for spatial memory. Rats with either selective, neurotoxic mammillary body lesions or discrete mammillothalamic tract lesions were tested on various spatial working memory tasks. Tests using the T-maze, radial-arm maze, and water maze were manipulated to compare three possible theories of mammillary body function by increasing proactive interference, increasing retention interval, and taxing the rapid processing of novel spatial stimuli. On T-maze alternation and radial-arm maze tasks, both lesion groups were initially impaired but seemed to recover. Transfer tests revealed, however, a more permanent change in performance, suggesting a failure to use distal (allocentric) cues. Consistent with this, both groups were also impaired at matching-to-place in the water maze and showed little improvement with practice. Nevertheless, once the lesion groups had been trained on a task, they were not affected differentially either by an increase of proactive interference or by retention intervals of up to 30 min. Although both mammillary body and mammillothalamic tract lesions resulted in similar impairments, the mammillothalamic tract group was the more affected when acquiring new spatial information. Together, these results suggest that mammillary body damage causes an encoding deficit when learning new spatial tasks, resulting in a suboptimal mode of performance, which may reflect a loss of directional heading information

Thanks for the memories: Extending the hippocampal-diencephalic mnemonic system [Letter]

The goal of our target article was to review a number of emerging facts about the effects of limbic damage on memory in humans and animals, and about divisions within recognition memory in humans. We then argued that this information can be synthesized to produce a new view of the substrates of episodic memory. The key pathway in this system is from the hippocampus to the anterior thalamic nuclei. There seems to be a general agreement that the importance of this pathway has previously been underestimated and that it warrants further study. At the same time, a number of key questions remain. These concern the relationship of this system to another temporal-lobe/diencephalic system that contributes to recognition, and the relationship of these systems to prefrontal cortex activity

Selective importance of the rat anterior thalamic nuclei for configural learning involving distal spatial cues

To test potential parallels between hippocampal and anterior thalamic function, rats with anterior thalamic lesions were trained on a series of biconditional learning tasks. The anterior thalamic lesions did not disrupt learning two biconditional associations in operant chambers where a specific auditory stimulus (tone or click) had a differential outcome depending on whether it was paired with a particular visual context (spot or checkered wall-paper) or a particular thermal context (warm or cool). Likewise, rats with anterior thalamic lesions successfully learnt a biconditional task when they were reinforced for digging in one of two distinct cups (containing either beads or shredded paper), depending on the particular appearance of the local context on which the cup was placed (one of two textured floors). In contrast, the same rats were severely impaired at learning the biconditional rule to select a specific cup when in a particular location within the test room. Place learning was then tested with a series of go/no-go discriminations. Rats with anterior thalamic nuclei lesions could learn to discriminate between two locations when they were approached from a constant direction. They could not, however, use this acquired location information to solve a subsequent spatial biconditional task where those same places dictated the correct choice of digging cup. Anterior thalamic lesions produced a selective, but severe, biconditional learning deficit when the task incorporated distal spatial cues. This deficit mirrors that seen in rats with hippocampal lesions, so extending potential interdependencies between the two sites

Qualitatively different hippocampal subfield engagement emerges with mastery of a spatial memory task by rats

The parallel, entorhinal cortex projections to different hippocampal regions potentially support separate mnemonic functions. To examine this possibility, rats were trained in a radial-arm maze task so that hippocampal activity could be compared after “early” (two sessions) or “late” (five sessions) learning. Induction of the immediate-early gene Zif268 was then measured, so revealing possible activity differences across hippocampal subfields andthe parahippocampal cortices. Each rat inthetwo experimental groups (early, late) was also yokedto a control ratthat obtainedthe same number of rewards, visitedthe same number of maze arms, and spent a comparable amount of time in the maze. Although overall Zif268 levels did not distinguish the four groups, significant correlations were found between spatial memory performance and levels of dentate gyrus Zif268 expression in the early but not the late training group. Conversely, hippocampalfields CA3 and CA1 Zif268 expression correlated with performance inthe late but notthe earlytraining group. This reversal inthe correlation pattern was echoed by structural equation modeling, which revealed dynamic changes in effective network connectivity.With early training,the dentate gyrus appearedto help determine CA1 activity, but by latetrainingthe dentate gyrus reduced its neural influence. Furthermore, CA1 was distinguished from CA3, each subfield developing opposite relations with task mastery. Thus, functional entorhinal cortex coupling with CA1 activity became more direct with additional training, so producing a trisynaptic circuit bypass. The present study reveals qualitatively different patterns of hippocampal subfield engagement dependent on task demands and mastery

Different contributions of the hippocampus and perirhinal cortex to recognition memory

Brain regions involved in visual recognition memory, including the hippocampus, have been investigated by measuring differential neuronal activation produced by novel and familiar pictures. Novel and familiar pictures were presented simultaneously, one to each eye, using a paired viewing procedure. Differential neuronal activation was determined using immunohistochemistry for the protein products of c-fos as an imaging technique. The results establish that the regions of the rat brain associated with discriminating the novelty or familiarity of an individual item (such as a single object) differ from those responding to a spatial array of items (such as a scene). Perirhinal cortex and area TE of the temporal lobe are activated significantly more by pictures of novel than of familiar individual objects, but the hippocampus is not differentially activated. In contrast, pictures of novel arrangements of familiar items produce significantly greater activation than familiar arrangements of these items in postrhinal cortex and subfield CA1 of the hippocampus but significantly less activation in the dentate gyrus and subiculum; perirhinal cortex and area TE are not differentially activated. Thus, the hippocampus is importantly involved in processing information essential to recognition memory concerning the relative familiarity of arrangements of items, as needed for episodic memory of scenes, whereas the perirhinal cortex processes such information for individual items

Functionally dissociating aspects of event memory: The effects of combined perirhinal and postrhinal lesions on object and place memory in the rat

Reciprocal interactions between the hippocampus and the perirhinal and parahippocampal cortices form core components of a proposed temporal lobe memory system. For this reason, the involvement of the hippocampus in event memory is thought to depend on its connections with these cortical areas. Contrary to these predictions, we found that NMDA-induced lesions of the putative rat homologs of these cortical areas (perirhinal plus postrhinal cortices) did not impair performance on two allocentric spatial tasks highly sensitive to hippocampal dysfunction. Remarkably, for one of the tasks there was evidence of a facilitation of performance. The same cortical lesions did, however, disrupt spontaneous object recognition and object discrimination reversal learning but spared initial acquisition of the discrimination. This pattern of results reveals important dissociations between different aspects of memory within the temporal lobe. Furthermore, it shows that the perirhinal–postrhinal cortex is not a necessary route for spatial information reaching the hippocampus and that object familiarity–novelty detection depends on different neural substrates than do other aspects of event memory