Biomedical subjects

E Passino

Publications and source records attributed to E Passino.

6 recordsLinked to original sources

PubMed2001

Learning about the context in genetically-defined mice.

Defective utilisation of background stimuli may result in a large range of cognitive impairments. We describe here three experimental paradigms taxing the processing of contextual information, (i) radial maze learning under distinct cueing conditions and successive context shifts; (ii) reactivity to spatial and object change; (iii) contextual versus cue fear conditioning with pre-test exposure to the experimental context. These paradigms have then been used to characterise the behaviour of null mutant and transgenic mice. In a first series of experiments, we assessed the effect of the null mutation of the gene encoding for Tissue Plasminogen Activator (tPA). Initial investigations pointed to a reduction of the late phase of long-term potentiation in tPA-knock out relative to wild type mice without any consistent performance impairment in several hippocampal-dependent tasks. When tested following our protocols, we found tPA knock out impaired in habituation of object exploration, reactivity to spatial change and contextual fear conditioning. The second example concerns mice overexpressing the mutant human Cu,Zn superoxide dismutase (SOD1) gene, that provide a murine model of amyotrophic lateral sclerosis. We found these mice exhibiting a paradoxical selective enhancement of reactivity to spatial change in comparison with mice overexpressing either the endogeneous murine Cu,Zn SOD1 or the wild type human Cu,Zn SOD1 genes. Our conclusion emphasises the view that experimental protocols involving contextual manipulations may be suitable for differentiating behavioural phenotypes.

Animals↗

PubMed2001

A synaptic mechanism underlying the behavioral abnormalities induced by manganese intoxication.

In the present study we have characterized a rat model of manganese (Mn) intoxication leading to behavioral disinhibition in the absence of major motor alterations. These behavioral changes were associated with significantly increased brain Mn levels but were uncoupled to anatomical lesions of the striatum or to morphological and cytochemical changes of the nigrostriatal dopaminergic pathway. The analysis of this model at cellular level showed an enhanced dopaminergic inhibitory control of the corticostriatal excitatory transmission via presynaptic D2-like dopamine (DA) receptors in slices obtained from Mn-treated rats. Conversely, the use of agonists acting on presynaptic purinergic, muscarinic, and glutamatergic metabotropic receptors revealed a normal sensitivity. Moreover, membrane responses recorded from single dopaminergic neurons following activation of D2 DA autoreceptors were also unchanged following Mn intoxication. Thus, our findings indicate a selective involvement of the D2-like DA receptors located on glutamatergic corticostriatal terminals in this pathological condition and suggest that the behavioral symptoms described in the "early" clinical phase of manganism may be caused by an abnormal dopaminergic inhibitory control on corticostriatal inputs. The identification of the synaptic mechanism underlying the "early" phase of Mn intoxication might have a critical importance to understand the causes of the progression of this pathological condition towards an "established" phase characterized by motor abnormalities and anatomical lesions of the basal ganglia.

Animals↗

PubMed2000

Contextual-dependent effects of nucleus accumbens lesions on spatial learning in mice.

The effect of nucleus accumbens lesions on radial maze performance of C57BL/6 and DBA/2 mice was assessed under distinct extra-maze cuing conditions. Among sham-lesioned mice, C57BL/6 performed better under rich than poor cuing conditions whereas DBA performed in the same fashion under both conditions. In C57BL/6, a disruptive effect of lesions was found only in mice tested under rich cuing. Conversely, in DBA/2, the lesions improved performance under poor cuing and disrupted performance under rich cuing. In that strain, a possible lesion-induced enhancement of attention to background stimuli improving performance under poor cuing but producing interference under rich cuing is suggested. In general, the lesions effect seemed to depend on the strain predisposition to implement configural or cue-based responding.

Animals↗

PubMed2000

Fear conditioning in C57/BL/6 and DBA/2 mice: variability in nucleus accumbens function according to the strain predisposition to show contextual- or cue-based responding.

The contribution of the nucleus accumbens shell, the dorsal hippocampus, and the basolateral amygdala to contextual and explicit cue fear conditioning was assessed in C57BL/6 (C57) and DBA/2 (DBA) mice showing differences in processing contextual information associated with consistent but non-pathological variations in hippocampal functionality. Mice from both strains with bilateral ibotenic acid or sham lesions located in each area were introduced in a conditioning chamber and exposed twice to the pairing of a tone (2 x 8 s, 2000 Hz, 80 dB) with a shock (2 s, 0.7 mA). On the following day, mice were first exposed to the training context then to the tone in a different context. Freezing behaviour was scored in all situations. C57 showed more freezing to the context than to the tone whereas DBA showed more freezing to the tone than to the context. In C57, both nucleus accumbens and hippocampal lesions impaired acquisition of contextual fear conditioning but paradoxically improved acquisition of cue fear conditioning, whereas amygdala lesions disrupted performance in every task. In DBA, nucleus accumbens lesions, like amygdala lesions, impaired acquisition of both contextual and cue fear conditioning, whereas hippocampal lesions did not produce any effect. The parallelism between the effect of nucleus accumbens and hippocampus lesions in C57, and between the effect of nucleus accumbens and amygdala lesions in DBA points to a variability in nucleus accumbens function according to the strain specialization to develop context- or cue-based responding.

Acoustic Stimulation↗

PubMed1999

Visual discrimination in inbred mice: strain-specific involvement of hippocampal regions.

Possible differences in functionality between the dorsal and the ventral regions of the hippocampus have been investigated in C57BL/6 (C57) and DBA/2 (DBA) inbred mice differing in their hippocampal anatomy. Mice from these two strains with large ventral, small ventral, small dorsal, or sham hippocampal lesions were tested in a visual discrimination radial maze task. Results first showed no strain difference in baseline performance. Examination of the lesion effects in the former strain (C57) revealed that the three lesions produced equivalent performance impairements. In the latter (DBA), ventral lesions, regardless of the size, were found to have a more deleterious effect than had the dorsal lesion. Thus, in C57 mice, the two regions were found to exert a similar control on performance, whereas in DBA mice, there was a modest involvement of the dorsal region associated with an extensive participation of the ventral region. The fact that. in DBA mice, the ventral area appears to be extensively involved when the dorsal hippocampus is poorly functioning suggests the existence of possible compensatory mechanisms between region-related specific operations and, consequently, some form of functional plasticity within the hippocampal formation.

Analysis of Variance↗

PubMed1998

N-methyl-D-aspartate receptors in the nucleus accumbens are involved in detection of spatial novelty in mice.

The aim of this study was to investigate the role played by intra-accumbens N-methyl-D-aspartate (NMDA) receptors in spatial information encoding. For this purpose, the effect of local administration of both competitive (AP-5) and non-competitive (MK-801) NMDA antagonists was assessed in a task designed to estimate the ability of rodents to encode spatial relationships between discrete stimuli. The task consists of placing mice in an open field containing five objects and, after three sessions of habituation, examining their reactivity to object displacement (spatial novelty) and object substitution (object novelty). The results show that both doses of MK-801 (0.15 and 0.3 microg/side) induced a selective impairment in the capability of mice to detect spatial novelty. A similar effect was obtained by injecting the low dose of the competitive antagonist AP-5 (0.1 microg/side), whereas the high dose (0.15 microg/side) abolished detection of both spatial and object novelty. Taken together, these results show that intra-accumbens injections of low doses of competitive and non-competitive NMDA antagonists can produce selective deficits in processing spatial information resembling those observed after hippocampal damage. Moreover, the fact that pharmacological treatments spare memory processes involved in habituation suggests that NMDA antagonists may interfere with the formation of spatial representations rather than producing memory deficits per se.

Animals↗