Paradoxical facilitatory effect of fornix lesions on acquisition of contextual fear conditioning in mice

Interval timing, the ability to encode and retrieve the memory of intervals from seconds to minutes, guides fundamental animal behaviors across the phylogenetic tree. In Pavlovian fear conditioning, an initially neutral stimulus (conditioned stimulus, CS) predicts the arrival of an aversive unconditioned stimulus (US, generally a mild foot-shock) at a fixed time interval. Although some studies showed that temporal relations between CS and US events are learned from the outset of conditioning, the question of the memory of time and its underlying neural network in fear conditioning is still poorly understood. The aim of the present study was to investigate the role of the dorsal striatum in timing intervals in odor fear conditioning in male rats. To assess th interval timing ability in this paradigm, we used the respiratory frequency. This enabled us to detect the emergence of temporal patterns related to the odor-shock time interval from the early stage of learning, confirming that rats are able to encode the odor-shock time interval after few training trials. We carried out reversible inactivation of the dorsal striatum before the acquisition session and before a shift in the learned time interval, and measured the effects of this treatment on the temporal pattern of the respiratory rate. In addition, using intracerebral microdialysis, we monitored extracellular dopamine level in the dorsal striatum throughout odor-shock conditioning and in response to a shift of the odor-shock time interval. Contrary to our initial predictions based 2 on the existing literature on interval timing, we found evidence suggesting that transient inactivation of the dorsal striatum may favor a more precocious buildup of the respiratory temporal pattern during the odor-shock interval in a manner that reflected the duration of the interval. Our data further suggest that the conditioning and the learning of a novel time interval were associated with a decrease in dopamine level in the dorsal striatum, but not in the nucleus accumbens. These findings prompt a reassessment of the role of the striatum and striatal dopamine in interval timing, at least when considering Pavlovian aversive conditioning.

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Section: Discussionsupporting

confidence: 92%

Dorsal striatum and the temporal expectancy of an aversive event in Pavlovian odor fear learning

Boulanger-Bertolus

Parrot

Doyère

et al. 2021

Neurobiology of Learning and Memory

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“…In line with the literature (Davis et al, 1989;Dìaz-Mataix et al, 2013;Drew et al, 2005;Dupin et al, 2020;Laurent-Demir & Jaffard, 2000;Ohyama et al, 2006;, our results support the assumption that learning a time interval happens early in conditioning, and further suggest that the expression of that learning can be modulated by the dorsal striatum. Indeed, inactivation of the dorsal striatum hastened 11 2C) were not associated with differences in the cannulas' placement (Figure S1), suggesting they may instead result from interindividual variability in timing abilities (see Dupin et al, 2020 for a discussion of timing abilities and associated brain dynamics).…”

Section: Discussionsupporting

confidence: 92%

Dorsal striatum and the temporal expectancy of an aversive event in Pavlovian odor fear learning

Boulanger-Bertolus

Parrot

Doyère

et al. 2021

Preprint

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Interval timing, the ability to encode and retrieve the memory of intervals from seconds to minutes, guides fundamental animal behaviors across the phylogenetic tree. In Pavlovian fear conditioning, an initially neutral stimulus (conditioned stimulus, CS) predicts the arrival of an aversive unconditioned stimulus (US, generally a mild foot-shock) at a fixed time interval. Although some studies showed that temporal relations between CS and US events are learned from the outset of conditioning, the question of the memory of time and its underlying neural network in fear conditioning is still poorly understood. The aim of the present study was to investigate the role of the dorsal striatum in timing intervals in odor fear conditioning in male rats. To assess the animal's interval timing ability in this paradigm, we used the respiratory frequency. This enabled us to detect the emergence of temporal patterns related to the odor-shock time interval from the early stage of learning, confirming that rats are able to encode the odor-shock time interval after few training trials. We carried out reversible inactivation of the dorsal striatum before the acquisition session and before a shift in the learned time interval, and measured the effects of this treatment on the temporal pattern of the respiratory rate. In addition, using intracerebral microdialysis, we monitored extracellular dopamine level in the dorsal striatum throughout odor-shock conditioning and in response to a shift of the odor-shock time interval. Contrary to our initial predictions based on the existing literature on interval timing, we found evidence suggesting that transient inactivation of the dorsal striatum may favor a more precocious buildup of the respiratory frequency's temporal pattern during the odor-shock interval in a manner that reflected the duration of the interval. Our data further suggest that the conditioning and the learning of a novel time interval were associated with a decrease in dopamine level in the dorsal striatum, but not in the nucleus accumbens. These findings prompt a reassessment of the role of the striatum and striatal dopamine in interval timing, at least when considering Pavlovian aversive conditioning.

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“…The lack of further increases in glutamate following the next pairings suggests that one pairing is sufficient for the induction of memory trace formation. Behavioral studies have already demonstrated that fear learning can be acquired in a single trial in rodents (Blanchard et al 1975;Bevins and Ayres 1995;Laurent-Demir and Jaffard 2000). However, it is important to stress that the absence of glutamate peaks from trials 2 to 6 does not mean that no glutamate at all was released during this period.…”

Section: Amino Acid Fluctuations In Basolateral Amygdalamentioning

confidence: 99%

Differential dynamics of amino acid release in the amygdala and olfactory cortex during odor fear acquisition as revealed with simultaneous high temporal resolution microdialysis

Hegoburu¹,

Sevelinges²,

Thévenet³

et al. 2009

Learn. Mem.

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Although the amygdala seems to be essential to the formation and storage of fear memories, it might store only some aspects of the aversive event and facilitate the storage of more specific sensory aspects in cortical areas. We addressed the time course of amygdala and cortical activation in the context of odor fear conditioning in rats. Using high temporal resolution (1-min sampling) intracerebral microdialysis, we investigated the dynamics of glutamate and GABA fluctuations simultaneously in basolateral amygdala (BLA) and posterior piriform cortex (pPCx) during the course of the acquisition session, which consisted of six odor (conditioned stimulus)-footshock (unconditioned stimulus) pairings. In BLA, we observed a transient increase in amino acid concentrations following the first odor-shock pairing, after which concentrations returned to baseline levels or slightly below. In pPCx, transient increases were seen after each pairing and were also observed after the last odor-shock pairing, corresponding to the predicted times of anticipated trials. Furthermore, we observed that for the first pairing, the increase in BLA occurred earlier than the increase in pPCx. These data suggest that the amygdala is engaged early during acquisition and precedes the activation of the olfactory cortex, which is maintained until the end of the session. In addition, our data raise the challenging idea that the olfactory cortex might store certain aspects of fear conditioning related to the timing of the associations.

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Paradoxical facilitatory effect of fornix lesions on acquisition of contextual fear conditioning in mice

Cited by 13 publications

References 31 publications

Dorsal striatum and the temporal expectancy of an aversive event in Pavlovian odor fear learning

Dorsal striatum and the temporal expectancy of an aversive event in Pavlovian odor fear learning

Dorsal striatum and the temporal expectancy of an aversive event in Pavlovian odor fear learning

Differential dynamics of amino acid release in the amygdala and olfactory cortex during odor fear acquisition as revealed with simultaneous high temporal resolution microdialysis

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