Biomedical subjects

Aline Desmedt

Publications and source records attributed to Aline Desmedt.

10 recordsLinked to original sources

PubMed2006

Extracellular hippocampal acetylcholine level controls amygdala function and promotes adaptive conditioned emotional response.

Ample data indicate that tone and contextual fear conditioning differentially require the amygdala and the hippocampus. However, mechanisms subserving the adaptive selection among environmental stimuli (discrete tone vs context) of those that best predict an aversive event are still elusive. Because the hippocampal cholinergic neurotransmission is thought to play a critical role in the coordination between different memory systems leading to the selection of appropriate behavioral strategies, we hypothesized that this cholinergic signal may control the competing acquisition of amygdala-mediated tone and contextual conditioning. Using pavlovian fear conditioning in mice, we first show a higher level of hippocampal acetylcholine release and a specific pattern of extracellular signal-regulated kinase 1/2 (ERK1/2) activation within the lateral (LA) and basolateral (BLA) amygdala under conditions in which the context is a better predictor than a discrete tone stimulus. Second, we demonstrate that levels of hippocampal cholinergic neurotransmission are causally related to the patterns of ERK1/2 activation in amygdala nuclei and actually determine the selection among the context or the simple tone the stimulus that best predicts the aversive event. Specifically, decreasing the hippocampal cholinergic signal not only impaired contextual conditioning but also mimicked conditioning to the discrete tone, both in terms of the behavioral outcome and the LA/BLA ERK1/2 activation pattern. Conversely, increasing this cholinergic signal not only disrupted tone conditioning but also promoted contextual fear conditioning. Hence, these findings highlight that hippocampal cholinergic neurotransmission controls amygdala function, thereby leading to the selection of relevant emotional information.

Acetylcholine↗

PubMed2006

Foreground contextual fear memory consolidation requires two independent phases of hippocampal ERK/CREB activation.

Fear conditioning is a popular model for investigating physiological and cellular mechanisms of memory formation. In this paradigm, a footshock is either systematically associated to a tone (paired conditioning) or is pseudorandomly distributed (unpaired conditioning). In the former procedure, the tone/shock association is acquired, whereas in the latter procedure, the context/shock association will prevail. Animals with chronically implanted recording electrodes show enhanced amplitude of the extracellularly recorded field EPSP in CA1 pyramidal cells for up to 24 h after unpaired, but not paired, fear conditioning. This is paralleled by a differential activation of the ERK/CREB pathway in CA1, which is monophasic in paired conditioning (0-15 min post-conditioning), but biphasic (0-1 h and 9-12 h post-conditioning) in unpaired conditioning as revealed by immunocytochemistry and Western blotting. Intrahippocampal injection of the MEK inhibitor U0126 prior to each phase prevents the activation of both ERK1/2 and CREB after unpaired conditioning. Block of any activation phase leads to memory impairment. We finally reveal that the biphasic activation of ERK/CREB activity is independently regulated, yet both phases are critically required for the consolidation of long-term memories following unpaired fear conditioning. These data provide compelling evidence that CA1 serves different forms of memory by expressing differential cellular mechanisms that are dependent on the training regime.

Animals↗

PubMed2005

A different recruitment of the lateral and basolateral amygdala promotes contextual or elemental conditioned association in Pavlovian fear conditioning.

Convergent data suggest dissociated roles for the lateral (LA) and basolateral (BLA) amygdaloid nuclei in fear conditioning, depending on whether a discrete conditioned stimulus (CS)-unconditional stimulus (US) or context-US association is considered. Here, we show that pretraining inactivation of the BLA selectively impaired conditioning to context. In contrast, inactivation of the LA disrupted conditioning to the discrete tone CS, but also either impaired or enhanced contextual conditioning, depending on whether the context was in the foreground or in the background. Hence, these findings refine the current model of the amygdala function in emotional learning by showing that the BLA and the LA not only differentially contribute to elemental and context-US association, but also promote, through their interaction, the most relevant of these two associations.

Acoustic Stimulation↗

PubMed2005

The MAPK pathway and Egr-1 mediate stress-related behavioral effects of glucocorticoids.

Many of the behavioral consequences of stress are mediated by the activation of the glucocorticoid receptor by stress-induced high levels of glucocorticoid hormones. To explore the molecular mechanisms of these effects, we combined in vivo and in vitro approaches. We analyzed mice carrying a brain-specific mutation (GR(NesCre)) in the glucocorticoid receptor gene (GR, also called Nr3c1) and cell lines that either express endogenous glucocorticoid receptor or carry a constitutively active form of the receptor (DeltaGR) that can be transiently induced. In the hippocampus of the wild-type [corrected] mice after stress, as well as in the cell lines, activation of glucocorticoid receptors greatly increased the expression and enzymatic activity of proteins in the MAPK signaling pathway and led to an increase in the levels of both Egr-1 mRNA and protein. In parallel, inhibition of the MAPK pathway within the hippocampus abolished the increase in contextual fear conditioning induced by glucocorticoids. The present results provide a molecular mechanism for the stress-related effects of glucocorticoids on fear memories.

Animals↗

PubMed2004

Intermediate precision study on a capillary electrophoretic method for chlortetracycline.

We describe an intermediate precision study on a capillary electrophoretic (CE) method for chlortetracycline. It is shown how in one setup the influence of the factors time, analyst, and equipment on the precision can be investigated. As different types of CE equipments were included, the transferability of the method could be examined. Both the qualitative and quantitative aspect of the method were investigated. It was shown that small adaptations in method conditions can have a large influence on the method transferability. Although the method could be transferred to different types of CE equipments, the precision of the method was found poor when the between-equipment variability was taken into account. Despite the use of an internal standard, the between injection variability was found rather high.

Chlortetracycline↗

PubMed2004

The amygdala and appraisal processes: stimulus and response complexity as an organizing factor.

The amygdala has been implicated in a variety of functions, ranging from attention to memory to emotion. In theories about the amygdala's role in conditioned fear, the lateral amygdala (LA) is the primary, perhaps unique, interface for incoming conditioned sensory stimuli and the central nucleus is the major output station. Recent studies indicate, however, that amygdala output pathways may be dissociated as a function of the type of conditioned fear behavior. Based on behavioral, electrophysiological and anatomical evidence, the present discussion proposes a modification of the traditional model of input pathways to the amygdala such that the LA activation as a sensory interface is limited to relatively simple, unimodal conditioned stimulus features whereas the basal amygdaloid nucleus (B) may serve as an amygdaloid sensory interface for complex, configural conditioned stimulus information. We further argue that the partition of amygdalar nuclei according to a complexity dimension appears to correspond both for input and output pathways and thus constitutes a common organizing factor in the functional anatomy of the amygdala. The extensive intra-amygdala wiring is assumed to underlie the computations necessary to perform behavioral decisions of various levels of complexity. Collectively, these results endow the amygdala with a more sophisticated role in guiding motivation and behavior.

Acoustic Stimulation↗

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.

Animals↗

PubMed2003

Differential pattern of cAMP response element-binding protein activation in the rat brain after conditioned aversion as a function of the associative process engaged: taste versus context association.

Ample data indicate that cAMP-response element-binding protein (CREB) is essential for the formation of long-term memory in various species and learning systems. This implies that activated CREB could delineate neuronal circuits that subserve items in memory, while leaving open the possibility that the specifics of CREB activation itself contribute to the specificity of the internal representation encoded by the relevant circuit. We describe here the differential activation of CREB in the rat brain as a function of two related yet distinct forms of aversive conditioning: conditioned taste aversion (CTA) and conditioned context aversion (CCA). We found that CTA induces strong CREB activation in the insular cortex (IC) and the lateral septum (LS), but not in the parietal cortex (PC) and the medial septum (MS). In contrast, CCA results in strong activation in the PC and MS, but not in the IC and LS. These findings are congruent with a model that links differential pattern of activity within the LS and the MS with the acquisition of elemental versus contextual conditioning and, more generally, with the notion that CREB activation delineates learning-dependent circuits as a function of the type of cognitive process engaged.

Animals↗

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

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.

Animals↗