Biomedical subjects

B Delatour

Publications and source records attributed to B Delatour.

9 recordsLinked to original sources

PubMed2006

The role of the rat prelimbic/infralimbic cortex in working memory: not involved in the short-term maintenance but in monitoring and processing functions.

Contrary to human and primate, working memory in the rodent is usually considered as a simple short term memory buffer and mainly investigated using delayed response paradigms. The aim of the present study was to further investigate the role of the rat prelimbic/infralimbic cortex in different spatial delayed tasks in order to dissociate its involvement in temporary storage from other information processes, such as behavioral flexibility and attention. In experiment 1 rats were trained in a standard elimination win-shift task in a radial-arm maze after which a 1-min delay was inserted mid trial. Prelimbic/infralimbic lesions induced only a transient disruption of performance following introduction of the delay. In experiment 2, rats were trained directly in a win-shift task with a 5-min delay that was subsequently extended to 30 min. Prelimbic/infralimbic lesions did not significantly affect behavior. Nevertheless, transient disruptions of performance (correlated with lesion extent) were noted repeatedly in lesioned rats when sets of interfering events were presented. The present findings indicate that prelimbic/infralimbic cortex is not directly involved in the short term maintenance of specific information but is implicated when changes, such as sudden introduction of a delay or exposure to unexpected interfering events, alter the initial situation. It appears that working memory in rodents should be considered, as in humans and primates, to encompass both storage and monitoring functions. The present results along with previous ones strongly suggest that prelimbic/infralimbic cortex is not involved in the temporary on-line storage but rather in the control of information required to prospectively organize the ongoing action.

Animals↗

PubMed2004

Alzheimer pathology disorganizes cortico-cortical circuitry: direct evidence from a transgenic animal model.

It has been proposed that Alzheimer disease (AD) is associated with a "disconnection syndrome" due to the gradual loss of morphological and functional integrity of cortico-cortical pathways. This hypothesis derives from indirect neuropathological observations, but definitive evidence that AD primarily targets cortico-cortical networks is still lacking. By means of neuroanatomical anterograde tracing methods, we have investigated, in a murine transgenic model of AD, the impact of the amyloid burden on axonal terminals in different neural systems. Axonal tracings revealed, in accordance with the "disconnection syndrome" hypothesis, that cortico-cortical fibers are significantly disorganized. Terminal fields in local and distant cortical areas contained numerous swollen dystrophic neurites often grouped in grape-like clusters at the plaque periphery. In contrary to fibers of cortical origin, those originating from subcortical brain structures only showed limited signs of degeneration upon reaching their cortical targets. These observations suggest a selective disruption of cortico-cortical connections induced by AD brain pathology.

Alzheimer Disease↗

PubMed2002

Projections from the parahippocampal region to the prefrontal cortex in the rat: evidence of multiple pathways.

The purpose of the present study was to investigate, by means of anterograde tracing methods, the detailed organization of the parahippocampal-prefrontal projections in the rat brain. Efferents from the perirhinal cortex were found to terminate principally in both the ventromedial (prelimbic and infralimbic cortices) and lateral (agranular insular cortex) regions of the prefrontal cortex. Terminal fields were observed mainly in the superficial layers of the prefrontal cortex. Projections arising from the dorsolateral entorhinal cortex, which borders the perirhinal cortex along its ventral extent, were similarly directed to the ventromedial and lateral prefrontal cortices but also encompassed other frontal areas (dorsomedial and orbital prefrontal regions). Terminal fields of entorhinal projections were also found in the superficial layers of the prefrontal cortex. A third pathway, taking its source in the post-rhinal cortex, presented striking topographical differences with the two other output systems. Hence, post-rhinal efferences terminated only in the ventrolateral orbital area. The results indicate that two main routes originate from the parahippocampal region to reach the prefrontal cortex. One pathway involves the rostral and lateral portions of the parahippocampal region (perirhinal and dorsolateral entorhinal cortices), and the other relies on its most caudal region, the post-rhinal cortex. The presence of such different multiple parahippocampal-prefrontal pathways may have functional relevance for learning and memory processes.

Animals↗

PubMed2001

Involvement of the dorsal anterior cingulate cortex in temporal behavioral sequencing: subregional analysis of the medial prefrontal cortex in rat.

We recently demonstrated that rats with dorsal anterior cingulate (ACd) cortical lesions were disrupted in the acquisition of a temporal Go/No-Go alternation task, suggesting either an involvement of this medial prefrontal subregion in sequencing temporally ordered behaviors or alternatively in more general response selection processes 'Gisquet-Verrier et al., Psychobiology 28 (2000) 248'. In the present study, the effects of ACd lesions were investigated in two different training situations. Both tasks involved response selection but only one of the two tasks required behavioral sequencing. In experiment 1, rats with ACd lesions were normally able to select Go and No-Go responses, when selection processes were based on a tone/light conditional rule that does not require temporal patterning. In experiment 2, ACd-lesioned rats were disrupted during the acquisition of a spatial alternation task that relies on temporal patterning. These results provide further evidence of ACd involvement in behavioral sequencing, regardless of the nature (spatial or non-spatial) of chained responses. A comparison of ACd lesions-induced effects with those obtained with lesions to the adjacent prelimbic-infralimbic area 'Delatour & Gisquet-Verrier, Behav. Neurosci. 110 (1996) 1282; Delatour & Gisquet-Verrier, Behav. Neurosci. 113 (1999) 941' reveals a double dissociation of these two regions that reflects a functional regionalization of the medial prefrontal cortex in the rat.

Animals↗

PubMed2001

FE65 in Alzheimer's disease: neuronal distribution and association with neurofibrillary tangles.

FE65, a protein expressed in the nervous system, has the ability to bind the C-terminal domain of the amyloid precursor protein. This suggests a role for FE65 in the pathogenesis of Alzheimer's disease (AD). The present study was conducted to find out if the distribution of FE65 immunoreactivity was affected during the course of AD, and to determine the degree of co-localization of FE65 with other proteins known to be involved in AD. Single immunoperoxidase-labeling experiments, conducted on six sporadic AD patients and six nondemented age-matched controls, showed that the proportion of volume occupied by FE65 immunoreactivity was not modified in the isocortex of AD patients. However, in hippocampal area CA4, increased FE65 immunoreactivity seemed to be associated with the severity of the disease. Double-immunofluorescent labeling did not show any clear co-localization of FE65 with the amyloid precursor protein. FE65 immunoreactivity was also absent from focal and diffuse deposits of the beta-amyloid peptide. Unexpectedly double labeling experiments showed a co-localization of FE65 and tau proteins in intracellular tangles. Ultrastructural observations confirmed that FE65 was associated with paired helical filaments.

Aged↗

PubMed2000

Functional role of rat prelimbic-infralimbic cortices in spatial memory: evidence for their involvement in attention and behavioural flexibility.

The involvement of the medial prefrontal cortex (mPFC), and more particularly the prelimbic and infralimbic cortices (PL-IL area), in spatial memory remains controversial. The present study investigates the effects of neurotoxic lesions restricted to the PL-IL area of the mPFC in rats trained in two different spatial tasks. In experiment 1, PL-IL lesioned rats showed normal acquisition of a delayed non-matching to position task. They were also able to plan their responses for a prospective strategy but were transiently disrupted when the initial delay was extended. In experiment 2, rats were trained to locate one baited box among 13 identical boxes distributed on a circular arena. Lesioned rats performed normally when trained from a single start position but were severely disrupted when four start positions were used. A probe trial showed this deficit was not due to failure to learn the goal location. The addition of a proximal cue signalling the goal box helped lesioned rats to directly open the goal box, but did not compensate for greater distances that they travelled to reach it. Results from both experiments indicate that the PL-IL area is directly involved neither in allocentric spatial representations nor prospective memory and is not specifically involved in working memory. This area seems more likely to be involved in both attentional processes and behavioural flexibility that may be important for processing information for working memory as well as for spatial memory.

Animals↗

PubMed1999

Lesions of the prelimbic-infralimbic cortices in rats do not disrupt response selection processes but induce delay-dependent deficits: evidence for a role in working memory?

Effects of neurotoxic lesions of the prelimbic-infralimbic cortex (PL-IL) were examined in rats performing 2 conditional tasks. PL-IL-lesioned rats showed normal acquisition of a visuospatial conditional discrimination in a Y maze as well as a tone-light conditional discrimination in an operant chamber, indicating that the PL-IL is not necessary for response selection processes. When the working memory load was subsequently increased in the tone-light conditional discrimination, rats with PL-IL lesions showed a delay-dependent disruption of performance. This suggests a role of the PL-IL in some working memory processes. However, the present results, considered along with previous studies, suggest that the PL-IL does not seem to be directly involved in the processes necessary to maintain specific items over a delay period but rather in the planning of forthcoming behavioral responses on the basis of previously acquired information.

Animals↗

PubMed1999

[Alzheimer's disease: lesions and their progression].

Alzheimer disease appears to be a stereotyped mode of reaction of the central nervous system to various types of aggression such as different mutations involving various proteins, trisomy 21 or repeated head trauma as in dementia pugilistica. Rather than a disease, it appears to be a clinicopathological syndrome due to various causes. Lesions may be considered under 3 headings: neurofibrillary pathology, A beta peptide deposits and loss (neuronal and synaptic). Neurofibrillary pathology includes the neurofibrillary tangle, the crown of the senile plaque and the neuropil threads. All those lesions are characterized by the same ultrastructure--i.e. the accumulation of paired helical filaments--and the same immunohistochemistry: they are labelled by antibodies directed against the tau proteins. The amyloid deposits, present in the core of the senile plaque and in the vascular walls, are made of a 40 to 42 amino-acids long peptide, named A beta, derived from the amyloid precursor protein (APP). Antibodies directed against the A beta peptide also label diffuse deposits that are devoid of the tinctorial affinities and of the biochemical properties of amyloid substances. Those diffuse deposits are insufficient to cause dementia since they may be observed in high density in aged people without intellectual deterioration. Neuronal loss occurs after neurofibrillary pathology. The role of the synaptic pathology remains discussed. Besides tau proteins, A beta peptide and APP, several other proteins may play an important role: apolipoprotein E which could act as a chaperone protein, inducing or facilitating the formation of amyloid, presenilins 1 and 2, mutated in some cases of familial Alzheimer disease, alpha-synuclein which is present in the Lewy bodies found in Parkinson disease and in dementia with Lewy bodies. The A beta deposits are diffusely distributed in the cerebral cortex; the neurofibrillary changes have a hierarchical distribution. The progression of the neurofibrillary pathology in the various cortical areas follow a stereotyped sequence that may help to grade the severity of the disease. Progression may take decades. The relations between aging and Alzheimer disease are still poorly understood. Frequency of Alzheimer type lesions in old people could suggest that they are the inevitable burden of age, but this has been discussed.

Aged↗

PubMed1996

Prelimbic cortex specific lesions disrupt delayed-variable response tasks in the rat.

The role of the prelimbic cortex (PL) in rats was investigated with excitotoxic lesions. PL lesions altered the alternation scores in spontaneous and reinforced spatial delayed-alternation tasks. PL lesions induced a delay in conditioning under a temporal go/no-go alternation schedule but not under a continuous food-reinforcement schedule in a runway. PL lesions had no effect on the acquisition of a standard radial-arm-maze task nor on a fixed-goal location task but disrupted the acquisition of a variable-goal location task in a radial-arm maze. The present results indicate that PL lesions replicated most of the behavioral deficits obtained with larger prefrontal lesions. PL lesions disrupted the acquisition of delayed-variable response tasks while leaving unaffected fixed-response tasks. These results are discussed in relation with a working-memory, a response-selection, and an attentional hypothesis.

Animals↗