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John P Aggleton

Publications and source records attributed to John P Aggleton.

At least 19 recordsLinked to original sources
PubMed2006

Neurotoxic lesions of the rat perirhinal and postrhinal cortices and their impact on biconditional visual discrimination tasks.

It has been argued that damage to the perirhinal cortex should impair visual discriminations when the stimuli have overlapping features. In Experiment 1, rats with perirhinal cortex lesions were trained on a series of visual discriminations in a water tank, culminating in a biconditional discrimination. No evidence was found of a perirhinal lesion deficit, although the same rats showed an object recognition deficit. In Experiment 2 the lesions were extended to involve both the perirhinal and postrhinal cortices in a new group of rats. An impairment was now found on acquisition of the biconditional task, but this was not specific as impairments were also found on two elemental visual discriminations. Taken together, the study failed to find evidence that the rat perirhinal cortex is necessary for configural visual discriminations and so revealed that some ambiguous visual discriminations can be learnt when this area is removed. Furthermore, there was no evidence that the parahippocampal region is selectively dedicated to configural learning, even though the loss of this area can impair the acquisition of some configural tasks.

Animals↗
PubMed2006

Interleaving brain systems for episodic and recognition memory.

Conflicting models persist over the nature of long-term memory. Crucial issues are whether episodic memory and recognition memory reflect the same underlying processes, and the extent to which various brain structures work as a single unit to support these processes. New findings that have resulted from improved resolution of functional brain imaging, together with recent studies of amnesia and developments in animal testing, reinforce the view that recognition memory comprises at least two independent processes: one recollective and the other using familiarity detection. Only recollective recognition appears to depend on episodic memory. Attempts to map brain areas supporting these two putative components of recognition memory indicate that they depend on separate, but interlinked, structures.

Amnesia, Anterograde↗
PubMed2006

The different effects on recognition memory of perirhinal kainate and NMDA glutamate receptor antagonism: implications for underlying plasticity mechanisms.

To investigate the involvement of different types of glutamate receptors in recognition memory, selective antagonists of NMDA and kainate receptors were locally infused into the perirhinal cortex of the rat temporal lobe. Such infusion of a selective kainate receptor antagonist produced an unusual pattern of recognition memory impairment: amnesia after a short (20 min) but not a long (24 h) delay. In contrast, antagonism of perirhinal NMDA glutamate receptors by locally infused AP-5 (2-amino-5-phosphonopentanoic acid) impaired recognition memory after the long but not the short delay. For both drugs, impairment was found when the drug was present during acquisition but not when it was present during retrieval. Experiments in vitro indicate that selective antagonism of NMDA receptors containing NR2A subunits blocks perirhinal long-term potentiation (LTP), whereas antagonism of NMDA receptors containing NR2B subunits blocks long-term depression (LTD). However, recognition memory after a 24 h delay was impaired only when both an NR2A and an NR2B antagonist were infused together, not when either was infused separately. These results establish that kainate receptors have a role in recognition memory that is distinct from that of NMDA receptors, that there must be at least two independent underlying memory mechanisms in the infused region, that this region and no other is necessary for both short-term and long-term familiarity discrimination, and that perirhinal-dependent long-term recognition memory does not rely solely on processes used in NMDA-dependent LTP or LTD (although it might be independently supported by components of each type of process with one substituting for the other).

Animals↗
PubMed2006

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.

Animals↗
PubMed2006

The importance of the rat hippocampus for learning the structure of visual arrays.

It has been assumed that the integrity of the rodent hippocampus is required for learning the spatial distribution of visual elements in an array. Formally assessing this assumption is, however, far from straightforward as standard tests are amenable to alternative strategies. In order to provide a stringent test of this ability rats were trained on three concurrent visual discriminations in a water tank in which the stimuli in each pair of discriminations contained exactly the same elements but they differed in their spatial arrangement e.g. A|B vs. its mirror image B/A. Such 'structural' discriminations are a specific subtype of 'configural' or 'nonlinear' tasks. Following acquisition half of the rats received hippocampal lesions and all rats were retrained on the structural discriminations. Hippocampal lesions impaired the ability to relearn these 'structural' discriminations. In contrast, two other groups of rats with similar hippocampal lesions showed no impairment on relearning two non-structural, configural discriminations: transverse patterning and biconditional learning. All three tasks used the same apparatus, the same stimulus elements, and similar training regimes. Superior performance by the rats with hippocampal lesions during a generalization decrement probe showed that hippocampal lesions had diminished sensitivity to 'structural' features on the biconditional task. While the rat hippocampus need not be required for all configural learning, it is important for the special case when the spatial arrangements of the elements are critical. This ability may be a prerequisite for the creation of mental snapshots, which underlie episodic memory.

Animals↗
PubMed2006

Novel temporal configurations of stimuli produce discrete changes in immediate-early gene expression in the rat hippocampus.

Changes in limbic brain activity in response to novel configurations of visual stimuli were assessed by quantifying two immediate-early genes, c-fos and zif268. Rats were first trained to use distal, visual cues to support radial-arm maze performance. Two separate sets of visual cues were used, one in the morning (Set A) and the other in the afternoon (Set B). On the final day the experimental group was tested with a novel configuration created by combining four of the eight visual cues from Set A with four of the eight visual cues from Set B. Although each individual cue was in a familiar location, the combination of cues was novel. Comparisons with a control group revealed discrete decreases in Fos centred in the hippocampus and retrosplenial cortex. The hippocampal c-fos findings produced a dissociation with the perirhinal cortex, where no change was observed. Other regions seemingly unaffected by the novel stimulus configuration included the postrhinal, entorhinal and parietal cortices. Zif268 levels in the experimental group increased in the anterior ventral thalamic nucleus. Although previous studies have shown how the rat hippocampus is involved in responding to the spatial rearrangement of visual stimuli, the present study examined temporal rearrangement. The selective immediate-early gene changes in the hippocampus and two closely related sites (retrosplenial cortex and anterior ventral thalamic nucleus) when processing the new stimulus configuration support the notion that the hippocampus is important for learning the 'relational' or 'structural' features of arrays of elements, be they spatial or temporal.

Animals↗
PubMed2005

Projections from the entorhinal cortex, perirhinal cortex, presubiculum, and parasubiculum to the medial thalamus in macaque monkeys: identifying different pathways using disconnection techniques.

The projections from the perirhinal cortex, entorhinal cortex, parasubiculum, and presubiculum to the thalamus were examined using both anterograde and retrograde tracers. Attention focused on the routes taken by these projections, which were delineated by combining surgical tract section with the placement of a tracer. Projections to the anterior thalamic nuclei almost exclusively used the fornix. These relatively light projections, which arose from all areas of the entorhinal cortex, from the presubiculum, parasubiculum, and area 35 of the perirhinal cortex, terminated mainly in the anterior ventral nucleus. In contrast, the projections to the lateral dorsal nucleus from the entorhinal cortex, presubiculum and parasubiculum were denser than those to the anterior thalamic nuclei. The projections to the lateral dorsal nucleus used two routes. While nearly all of the projections from the subicular complex used the fornix, many of the entorhinal cortex projections passed caudally in the temporopulvinar bundle to reach the lateral dorsal nucleus. The perirhinal cortex, as well as the entorhinal cortex, also projects to nucleus medialis dorsalis. These projections exclusively used the external capsule and thence the inferior thalamic peduncle. Other temporal-thalamic projections included those to the medial pulvinar, via the temporopulvinar bundle, from the perirhinal and entorhinal cortices, and those to the paraventricular nucleus from the entorhinal cortex. By identifying these routes, it is possible to appreciate how different lesions might disconnect temporal-diencephalic pathways and so contribute to memory disorders.

Amidines↗
PubMed2005

cAMP responsive element-binding protein phosphorylation is necessary for perirhinal long-term potentiation and recognition memory.

We established the importance of phosphorylation of cAMP responsive element-binding protein (CREB) to both the familiarity discrimination component of long-term recognition memory and plasticity within the perirhinal cortex of the temporal lobe. Adenoviral transduction of perirhinal cortex (and adjacent visual association cortex) with a dominant-negative inhibitor of CREB impaired the preferential exploration of novel over familiar objects at a long (24 h) but not a short (15 min) delay, disrupted the normal reduced activation of perirhinal neurons to familiar compared with novel pictures, and impaired long-term potentiation of synaptic transmission in perirhinal slices. The consistency of these effects across the behavioral, systems, and cellular levels of analysis provides strong evidence for involvement of CREB phosphorylation in synaptic plastic processes within perirhinal cortex necessary for long-term recognition memory.

Adenoviridae↗
PubMed2005

Sparing of the familiarity component of recognition memory in a patient with hippocampal pathology.

Subject KN has a persistent anterograde amnesia as a result of brain injury following meningitis in 1993. MRI scans reveal a bilateral decrease in the volume of his hippocampal region (dentate gyrus, CA1-4, subicular cortices) of approximately 45% in both the right and left hemispheres, although the volume of his perirhinal cortex appears normal. Aside from some changes to his occipital lobe and bilateral shrinkage of the amygdala, the rest of his brain appears normal on recent quantitative MRI scans. A striking feature of his memory loss is his ability to perform at normal levels on some tests of recognition, despite his consistent deficit on tests of recall. Two tests designed specifically to distinguish performance of two putative divisions of recognition memory (the Remember/Know procedure and the use of receiver operating characteristics to distinguish familiarity and recollection), provide evidence for a selective sparing of the familiarity component of recognition. The dissociation within recognition memory supports dual-process models of recognition, and also supports proposals that anatomically linked regions within the medial temporal lobe make qualitatively different contributions to recognition.

Adult↗
PubMed2005

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.

Animals↗
PubMed2005

Projections from the hippocampal region to the mammillary bodies in macaque monkeys.

A combination of anterograde and retrograde tracers mapped the direct hippocampal and parahippocampal inputs to the mammillary bodies in two species of macaque monkey. Dense projections arose from pyramidal cells in layer III of the subiculum and prosubiculum, and terminated in the medial mammillary nucleus. While there was no evidence of an input from the dentate gyrus or fields CA1-3, a small contribution arose from the presubiculum and entorhinal cortices. All of the hippocampal and parahippocampal projections to the mammillary bodies appeared to use the fornix as a route. The caudal portions of the subiculum and prosubiculum contained the greatest numbers of cells projecting to the mammillary bodies. A light contralateral projection to the medial mammillary nucleus was also observed, although this appeared to arise primarily from the more rostral portions of the subiculum and prosubiculum. There was a crude topography within the medial mammillary nucleus, with the caudal subicular projections terminating in the mid and dorsal portions of the nucleus while the rostral subicular and entorhinal projections terminated in the ventral and lateral portions of the medial nucleus. Light ipsilateral projections throughout the lateral mammillary nucleus were sometimes observed. Comparisons with related studies of the macaque brain showed that the dense hippocampal projections to the mammillary bodies arise from a population of subicular cells separate from those that project to the anterior thalamic nuclei, even though the major output from the mammillary bodies is to the anterior thalamic nuclei. Other comparisons revealed underlying similarities with the corresponding projections in the rat brain.

Amino Acids↗
PubMed2004

Testing the importance of the retrosplenial guidance system: effects of different sized retrosplenial cortex lesions on heading direction and spatial working memory.

The present study: (1) tested the importance of the retrosplenial cortex for learning a specific heading direction and distance and, (2) determined if lesion size could explain apparent inconsistencies in the results of different research groups. Dark agouti rats received either 'complete' cytotoxic retrosplenial cortex lesions or 'standard' lesions, the latter sparing the caudal retrosplenial cortex. Animals were first tested on two versions of a "landmark" task in a water maze. In condition 1 animals could use both heading direction and allocentric position, while in condition 2 only heading direction was effective. In condition 1, animals with complete retrosplenial lesions were impaired by the end of training, their profile of performance being consistent with a failure to use allocentric position information. When the water maze task changed (condition 2) so that allocentric cues became redundant, the animals with complete retrosplenial lesions were able to head in the appropriate direction although they showed longer swim paths. Subsequent testing in the radial-arm maze provided more evidence that retrosplenial lesions can disrupt the use of distal (allocentric) room cues. The impairments seen with retrosplenial lesions were often mild but throughout the study performance of rats with 'complete' lesions was more disrupted than those with 'standard' lesions, who often did not differ from the controls. These findings show that lesion size is a critical factor and may explain why some studies have failed to find comparable deficits after retrosplenial cortex lesions.

Animals↗
PubMed2004

Chewing gum can produce context-dependent effects upon memory.

Two experiments examined whether chewing spearmint gum can affect the initial learning or subsequent recall of a word list. Comparing those participants in Experiment 1 who chewed gum at the learning or the recall phases showed that chewing gum at initial learning was associated with superior recall. In addition, chewing gum led to context-dependent effects as a switch between gum and no gum (or no gum and gum) between learning and recall led to poorer performance. Experiment 2 provided evidence that sucking gum was sufficient to induce some of the same effects as chewing.

Adult↗
PubMed2004

Testing the importance of the retrosplenial navigation system: lesion size but not strain matters: a reply to Harker and Whishaw.

In their review on the retrosplenial cortex Harker and Whishaw [Neurosci Biobehav Rev, 2004] claim that there is continued disagreement over the importance of this region for navigation. They argue that discrepancies in the published effects of retrosplenial lesions reflect two principal variables, choice of rat strain and choice of spatial task. In this reply, evidence is provided showing that Harker and Whishaw [Neurosci Biobehav Rev, 2004] have created a misleading impression and, in fact, there is a clear consensus that the rat retrosplenial cortex is necessary for navigation. Likewise, there is no dispute that the effects of retrosplenial lesions will differ for different tests of spatial learning. While Harker and Whishaw [Neurosci Biobehav Rev, 2004] also conclude that choice of rat strain has a critical impact on whether a lesion-induced deficit is found, a comprehensive review of the published data shows no systematic strain difference. There is, however, growing evidence that when interpreting the effects of retrosplenial lesions, account should be given of the lesion method and its interaction with lesion size.

Animals↗
PubMed2004

When is the perirhinal cortex necessary for the performance of spatial memory tasks?

The perirhinal cortex and hippocampus have close anatomical links and it has, therefore, been proposed that they have important, coordinated roles in memory. This review examines the relative role of these structures in spatial memory tasks that are known to be hippocampal-dependent. The published lesion data gives a mixed picture, as only some studies detect spatial deficits after perirhinal cortex lesions. The possible reasons for these inconsistencies are reviewed, along with electrophysiological data that indicate how perirhinal cortex lesions may alter neuronal activity in the hippocampus. Overall, the disruptive effects of perirhinal lesions on spatial memory performance are, when they occur, typically transient and never as severe as those seen after hippocampal lesions. It is argued that parallel cortical routes provide key, sensory data to the hippocampus such that in the absence of the perirhinal cortex alternative information is available. The deficits associated with perirhinal damage may then reflect difficulties that arise when task performance requires the use of ambiguous distal cues, for example, those containing overlapping visual features.

Electrophysiology↗
PubMed2004

Anterior thalamic lesions stop immediate early gene activation in selective laminae of the retrosplenial cortex: evidence of covert pathology in rats?

Lesions involving the anterior thalamic nuclei stopped immediate early gene (IEG) activity in specific regions of the rat retrosplenial cortex, even though there were no apparent cytoarchitectonic changes. Discrete anterior thalamic lesions were made either by excitotoxin (Experiment 1) or radiofrequency (Experiment 2) and, following recovery, the rats foraged in a radial-arm maze in a novel room. Measurements made 6-12 weeks postsurgery showed that, in comparison with surgical controls, the thalamic lesions produced the same, selective patterns of Fos changes irrespective of method. Granular (caudal granular cortex and rostral granular cortex), but not dysgranular (dysgranular cortex), retrosplenial cortex showed a striking loss of Fos-positive cells. While a loss of between 79 and 89% of Fos-positive cells was found in the superficial laminae, the deeper layers appeared normal. In Experiments 3 and 4, rats 9-10 months postsurgery were placed in an activity box for 30 min. Anterior thalamic lesions (Experiment 3) led to a pronounced IEG decrease of both Fos and zif268 throughout the retrosplenial cortex that now included the dysgranular area. These IEG losses were found even though the same regions appeared normal using standard histological techniques. Lesions of the postrhinal cortex (Experiment 4) did not bring about a loss of retrosplenial IEG activity even though this region is also reciprocally connected with the retrosplenial cortex. This selective effect of anterior thalamic damage upon retrosplenial activity may both amplify the disruptive effects of anterior thalamic lesions and help to explain the posterior cingulate hypoactivity found in Alzheimer's disease.

Animals↗
PubMed2003

Distinct patterns of hippocampal formation activity associated with different spatial tasks: a Fos imaging study in rats.

Fos levels were measured in rats trained in one of two qualitatively different spatial memory tasks in a water maze. In one task, ( landmark condition) rats found a submerged platform that was always 25 cm south of a visible landmark, the absolute position of the platform and landmark changing after every trial. In the other task ( place condition), rats swam to a platform that remained in the same absolute position on every session, but changed session to session, with this task relying on the memory of allocentric cues. Despite matched swim times, the landmark condition resulted in higher levels of Fos in a wide range of cortical and subcortical sites, including the hippocampus and its connections. Structural equation modelling revealed two different patterns of hippocampal function. In the allocentric place task there was a significant association between Fos activity in the entorhinal cortices and the hippocampus proper, while in the non-allocentric landmark task this relationship was not present, but was replaced by a connection from the entorhinal cortices to the subiculum. Thus, the two different tasks engage two different modes of hippocampal activity as demonstrated by Fos expression.

Animals↗