Biomedical subjects

John P Aggleton

Publications and source records attributed to John P Aggleton.

29 records · Page 2Linked to original sources

PubMed2003

Cholinergic neurotransmission is essential for perirhinal cortical plasticity and recognition memory.

We establish the importance of cholinergic neurotransmission to both recognition memory and plasticity within the perirhinal cortex of the temporal lobe. The muscarinic receptor antagonist scopolamine impaired the preferential exploration of novel over familiar objects, disrupted the normal reduced activation of perirhinal neurones to familiar compared to novel pictures, and blocked production of long-term depression (LTD) but not long-term potentiation (LTP) of synaptic transmission in perirhinal slices. The consistency of these effects across the behavioral, systems, and cellular levels of analysis provides strong evidence for the involvement of cholinergic mechanisms in synaptic plastic processes within perirhinal cortex that are necessary for recognition memory.

Animals↗

PubMed2003

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.

Animals↗

PubMed2003

Testing the importance of the caudal retrosplenial cortex for spatial memory in rats.

Although there is evidence to suggest that the retrosplenial cortex is involved in spatial learning and memory, many lesion studies have left the more caudal part of this region intact so leaving its role untested. In the first experiment, rats with neurotoxic lesions of the caudal half of the retrosplenial cortex (RspC1) were tested on a reference memory task in the water-maze. The RspC1 animals were impaired on initial acquisition although they performed normally on a subsequent probe test. The second experiment looked at working memory in the radial-arm maze and water-maze. Animals with caudal retrosplenial lesions (RspC2) were unimpaired on the acquisition stage of the radial-arm maze task but were impaired when the task involved maze rotation to control for the possible use of intramaze cues. The RspC2 animals also took longer to learn the platform position on a delayed matching-to-place task in the water-maze. These results show a subtle impairment in spatial memory performance that is not as severe as that seen when more complete lesions of the retrosplenial cortex are made.

Animals↗

PubMed2003

Evolutionary coherence of the mammalian amygdala.

Despite great interest in the role of the amygdala in animal and human behaviour, its very existence as a structurally and functionally unified brain component has been questioned, on the grounds that cell groups within it display divergent pharmacological and connectional characteristics. We argue that the question of whether particular brain nuclei constitute a valid structural and functional unit is inherently an evolutionary question, and we present a method for answering it. The method involves phylogenetic analysis of comparative data to determine whether or not separate regions of the putative brain structure show statistically correlated evolution. We find that, in three separate groups of mammals (primates and two groups of insectivores), evolutionary changes in the volumes of amygdala components are strongly correlated, even after controlling for volumetric change in a wide range of limbic and other brain structures. This allows us to reject the strong claim that the amygdala is neither a structural nor a functional unit, and demonstrates the importance of evolutionary analysis in resolving such issues in systems neuroscience.

Amygdala↗

PubMed2003

Lesions of the mammillothalamic tract impair the acquisition of spatial but not nonspatial contextual conditional discriminations.

This study examined the influence of selective mammillothalamic tract lesions in rats on the acquisition of two kinds of contextual conditional discrimination: one involving two contexts (A and B) that differed in their visuo-spatial properties and another involving two contexts (C and D) that differed in temperature. In contexts A (and C) presentations of a tone were paired with food whereas presentations of a clicker were not; and in contexts B (and D) presentations of the clicker were paired with food whereas those of the tone were not. Mammillothalamic tract lesions disrupted initial acquisition of the conditional discrimination involving visual contexts (A and B), but not the formally equivalent discrimination involving thermal contexts (C and D). These results provide support for the suggestion that mammillothalamic tract lesions disrupt visuo-spatial encoding.

Acoustic Stimulation↗

PubMed2002

Comparison of hippocampal, amygdala, and perirhinal projections to the nucleus accumbens: combined anterograde and retrograde tracing study in the Macaque brain.

A combination of anterograde and retrograde tracing techniques was used to study the projections to the nucleus accumbens from the amygdala, the hippocampal formation (including the entorhinal cortex), and the perirhinal cortex in two species of macaque monkey. To help identify possible subregions within the nucleus accumbens, the distribution of calbindin was examined in two additional monkeys. Although this revealed evidence of "core"- and "shell"-like regions within the accumbens, these different regions could not consistently be related to cytoarchitectonic features. The rostral amygdala sent nearly equivalent projections to both the medial and the lateral portions of nucleus accumbens, whereas projections arising from the middle and caudal amygdala terminated preferentially in the medial division of nucleus accumbens. The basal nucleus was the major source of these amygdala efferents, and there was a crude topography as parts of the basal and accessory basal nuclei terminated in different parts of nucleus accumbens. The subiculum was the major source of hippocampal projections to the nucleus accumbens, but some hippocampal efferents also originated in the parasubiculum, the prosubiculum, the adjacent portion of CA1, and the uncal portion of CA3. These hippocampal projections, which coursed through the fornix, showed a rostrocaudal gradient as more arose in the rostral hippocampus. Hippocampal efferents terminated most densely in the medial and ventral portions of nucleus accumbens, along with light label in the adjacent olfactory tubercle. The entorhinal projections were more evenly distributed between the medial nucleus accumbens and the olfactory tubercle, whereas the perirhinal projections were primarily to the olfactory tubercle. These cortical inputs were less reliant on the fornix. Amygdala and subicular (hippocampal) projections overlapped most completely in the medial division of nucleus accumbens.

Amygdala↗

PubMed2002

Physiological evidence for a possible projection from dorsal subiculum to hippocampal area CA1.

The substantial forward projection from hippocampal area CA1 to the subiculum has been comprehensively described, both anatomically and neurophysiologically. There are few data, however, regarding the existence of a backward projection from the subiculum to area CA1. We present here new electrophysiological evidence for the existence of this projection. We demonstrate a positive-going deflection in the evoked synaptic response in area CA1 following stimulation in dorsal subiculum. We also found a small, but significant, paired-pulse facilitatory effect at a 100-ms interstimulus interval. We were unable to induce long-term potentiation following high-frequency stimulation, but were able to induce short-term potentiation.

Animals↗

PubMed2002

Fos imaging reveals that lesions of the anterior thalamic nuclei produce widespread limbic hypoactivity in rats.

Activity of the immediate early gene c-fos was compared in rats with neurotoxic lesions of the anterior thalamic nuclei and in surgical controls. Fos levels were measured after rats had been placed in a novel room and allowed to run up and down preselected arms of a radial maze. An additional control group showed that in normal rats, this exposure to a novel room leads to a Fos increase in a number of structures, including the anterior thalamic nuclei and hippocampus. In contrast, rats with anterior thalamic lesions were found to have significantly less Fos-positive cells in an array of sites, including the hippocampus (dorsal and ventral), retrosplenial cortex, anterior cingulate cortex, and prelimbic cortex. These results show that anterior thalamic lesions disrupt multiple limbic brain regions, producing hypoactivity in sites associated in rats with spatial memory. Because many of the same sites are implicated in memory processes in humans (e.g., the hippocampus and retrosplenial cortex), this hypoactivity might contribute to diencephalic amnesia.

Animals↗

PubMed2002

Changes in Fos expression in the rat brain after unilateral lesions of the anterior thalamic nuclei.

Activity of the immediate early gene c-fos was compared across hemispheres in rats with unilateral anterior thalamic lesions. Fos protein was quantified after rats performed a spatial working memory test in the radial-arm maze, a task that is sensitive to bilateral lesions of the anterior thalamic nuclei. Unilateral anterior thalamic lesions produced evidence of a widespread hippocampal hypoactivity, as there were significant reductions in Fos counts in a range of regions within the ipsilateral hippocampal formation (rostral CA1, rostral dentate gyrus, 'dorsal' hippocampus, presubiculum and postsubiculum). A decrease in Fos levels was also found in the rostral and caudal retrosplenial cortex but not in the parahippocampal cortices or anterior cingulate cortices. The Fos changes seem most closely linked to sites that are also required for successful task performance, supporting the notion that the anterior thalamus, retrosplenial cortex and hippocampus form key components of an interdependent neuronal network involved in spatial mnemonic processing.

Animals↗

PubMed2002

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.

Animals↗

PubMedDate not supplied

Contrasting hippocampal and perirhinal cortex function using immediate early gene imaging.

The perirhinal cortex and hippocampus have close anatomical links, and it might, therefore, be predicted that they have close, interlinked roles in memory. Lesion studies have, however, often failed to support this prediction, providing dissociations and double dissociations between the two regions on tests of object recognition and spatial memory. In a series of rat studies we have compared these two regions using the expression of the immediate early gene c-fos as a marker of neuronal activity. This gene imaging approach makes it possible to assess the relative involvement of different brain regions and avoids many of the limitations of the lesion approach. A very consistent pattern of results was found as the various hippocampal subfields but not the perirhinal cortex show increased c-fos activity following tests of spatial learning. In contrast, the perirhinal cortex but none of the hippocampal subfields show increased c-fos activity when presented with novel rather than familiar visual objects. When novel scenes are created by the spatial rearrangement of familiar objects it is the hippocampus and not the perirhinal cortex that shows c-fos changes. This double dissociation for gene expression accords with that found from lesion studies and highlights the different contributions of the perirhinal cortex and hippocampus to memory.

Animals↗