Biomedical subjects

Robert Jaffard

Publications and source records attributed to Robert Jaffard.

5 recordsLinked to original sources

PubMed2003

An 8-day extensive elemental, but not contextual, fear conditioning potentiates hippocampal-lateral septal synaptic efficacy in mice.

Previous findings have suggested a critical role for hippocampal-lateral septal (HPC-LS) synaptic transmission in the modulation of elemental vs. contextual fear conditioning. Pharmacologically- or electrophysiologically-induced increases in HPC-LS neurotransmission were shown to be associated with both an increase in elemental and a decrease in contextual fear conditioning. However, elemental conditioning, induced by an unconditional stimulus (US) that was explicitly paired with a simple conditional stimulus (CS), did not result in any change in this neurotransmission when two tone CS-footshock US pairings were provided. The present experiment was thus designed to investigate directly, in mice, whether extensive elemental conditioning (repeated CS-US pairings) could induce an increase in HPC-LS neurotransmission. For that purpose, over 8 days, an elemental conditioning group was repeatedly submitted to CS-US pairings in either one context (A) or another (B) depending on the training day. Hence, whichever the context, the tone CS was the relevant predictive stimulus for the occurrence of the footshock US. In contrast, a contextual conditioning group was submitted to the same regimen except that the US was delivered only in context A and was never paired with the CS, making, thereby, the context A the relevant predictor for the US regardless of the occurrence of the tone CS. Results show that during re-exposure of the animals to either context A or B, a significant increase in HPC-LS neurotransmission was selectively associated with the repeated elemental conditioning. This study supports the idea that changes in HPC-LS neurotransmission may modulate the strength of simple CS-US associations, and suggests that alterations of hippocampal functioning might be involved.

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PubMed2003

Chronic ethanol consumption restores the age-related decrease in neurogranin mRNA level in the hippocampus of mice.

Neurogranin (Ng) is a Ca(2+)-sensitive calmodulin-binding neuron-specific protein that has been implicated in the regulation of numerous post-synaptic signalling pathways. Here, we investigate the effects of 5 months low level ethanol consumption (approximately 20% of total calories intake) on Ng mRNA expression in the brain of adult (approximately 7-8 months) and aged (approximately 21-22 months) mice using in situ hybridization histochemistry. Results showed that ageing was accompanied by a decrease in amounts of mRNA coding for Ng, especially in the hippocampus (approximately 25% of adults) known to play a critical role in higher cognitive functions. Chronic ethanol consumption restored this decline up to pre-senescent (adult) levels without altering Ng mRNA levels in adult mice. On the basis of recent data indicating a central role for Ng in the regulation of hippocampal synaptic plasticity and spatial learning, our results suggest that moderate ethanol consumption might have a beneficial influence on cognitive deterioration during senescence. Such a possibility is in fact congruent with recent follow-up studies conducted in elderly people.

Aging↗

PubMed2003

Hippocampal lesions and discrimination performance of mice in the radial maze: sparing or impairment depending on the representational demands of the task.

The effects of ibotenate hippocampal lesions on discrimination performance in an eight-arm radial maze were investigated in mice, using a three-stage paradigm in which the only parameter that varied among stages was the way the arms were presented. In the initial learning phase (stage 1), animals learned the valence or reward contingency associated with six (three positive and three negative) adjacent arms of the maze using a successive (go/no-go) discrimination procedure. In the first test phase (stage 2), the six arms were grouped into three pairs, so that on each trial, the subject was faced with a choice between two adjacent arms of opposite valence (concurrent two-choice discrimination). In the second test phase (stage 3), the subject was faced with all six arms simultaneously (six-choice discrimination). Hippocampal-lesioned mice acquired the initial learning phase at a near-normal rate but behaved as if they had learned nothing when challenged with the two-choice discriminations at stage 2. In contrast, they behaved normally when confronted with the six-choice discrimination at stage 3. Detailed examination of within- and between-stage performance suggests that hippocampal-lesioned mice perform as intact mice when presentation of the discriminanda encourages the storage and use of separate representations (i.e., in initial learning and six-choice discrimination testing), but that they fail in test situations that involve explicit comparisons between such separate representations (two-choice discriminations), hence requiring the use of relational representations.

Algorithms↗

PubMed2003

Fos imaging reveals ageing-related changes in hippocampal response to radial maze discrimination testing in mice.

A two-stage radial arm maze (RAM) task has been designed recently to demonstrate a specific age-related memory deficit in mice. It highlights the contrast between normal and deficient memory expression in a spatial discrimination problem depending on how to-be discriminated arms were presented to the animal. This specific deficit has been interpreted as a preferential loss in a relational/declarative form of memory, thereby implying an underlying hippocampal dysfunction. To test this hypothesis, neuronal activation measured by Fos immunostaining was compared in aged (21-23 months) and adult (4-6 months) mice trained in the aforementioned task and killed after a retention session consisting in age-insensitive probe trials, performed 6 days later (6-day RAM). Two comparison conditions were included: (i) repeated locomotor training on a treadmill (TM); (ii) the same RAM training, except for the use of a longer (30 days instead of six) retention interval (30-day RAM). Although all RAM groups displayed similar levels of performance at the end of the experiment, immediately before the mice were killed, significant between-group differences in brain activation were observed. In adult mice, 6-day RAM testing was associated with greater septal and hippocampal (CA1, CA3, DG) Fos expression than the TM condition. Lengthening the retention interval from 6 days to 30 days resulted in a significant decrease in RAM testing-induced Fos expression in most of the septo-hippocampal regions. With respect to adult mice, aged mice displayed reduced Fos expression (except for DG) and a lack of interrelationships between levels of Fos produced in each of the SH regions, in the 6-day RAM testing condition. Conversely, there was no effect of ageing on Fos expression associated with either TM training or 30-day RAM testing. These results are interpreted as reflecting age- (or time-) related alterations in recruiting of brain structures that underlie a relational/declarative form of memory expression.

Aging↗

PubMed2003

The effects of ibotenic hippocampal lesions on discriminative fear conditioning to context in mice: impairment or facilitation depending on the associative value of a phasic explicit cue.

To what extent the hippocampus is required for contextual conditioning remains a matter of debate. The present experiments examined the effects of ibotenate hippocampal lesions on discriminative fear conditioning to context in mice using measures of freezing in two conditioning paradigms. In both paradigms animals received foot shock as the unconditional stimulus (US) when placed in the (conditioning) context and no foot-shock when placed in the other (neutral) context. In both contexts, animals were presented with a tone as the conditioned stimulus (CS). In the conditioning context there was either no interval (delay condition) or a 30-s interval (trace condition) between tone CS end and shock US onset. These two paradigms were used because theory predicts that in the trace condition animals would learn more about contextual cues as predictors, or not, of shock US occurrence than in the delay condition. In agreement with this, we observed that sham-operated mice learned the context discrimination faster in the trace than in the delay condition. Lesions of the hippocampus significantly retarded, but did not prevent, the acquisition of the context discrimination in the trace condition. In contrast, lesions produced an opposite (facilitatory) effect in the delay condition, which was mainly observed during tone CS presentation. The data suggest that mice used two distinct competing strategies in solving this discrimination task: (i) a strategy relying on the processing of background contextual stimuli allowing direct establishment of context-US associations of different strengths, and (ii) a conditional cue (tone)-based strategy. Hence, hippocampal lesions may impair the use of the former strategy while exacerbating (unmasking) the use of the latter.

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