Respiration and brain neural dynamics associated with interval timing during odor fear learning in rats

Abstract

In fear conditioning, where a conditioned stimulus predicts the arrival of an aversive stimulus, the animal encodes the time interval between the two stimuli. Here we monitored respiration to visualize anticipatory behavioral responses in an odor fear conditioning in rats, while recording theta (5–15 Hz) and gamma (40–80 Hz) brain oscillatory activities in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), dorsomedial striatum (DMS) and olfactory piriform cortex (PIR). We investigated the temporal patterns of respiration frequency and of theta and gamma activity power during the odor-shock interval, comparing two interval durations. We found that akin to respiration patterns, theta temporal curves were modulated by the duration of the odor-shock interval in the four recording sites, and respected scalar property in mPFC and DMS. In contrast, gamma temporal curves were modulated by the interval duration only in the mPFC, and in a manner that did not respect scalar property. This suggests a preferential role for theta rhythm in interval timing. In addition, our data bring the novel idea that the respiratory rhythm might take part in the setting of theta activity dynamics related to timing.

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

“…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 behavioral adaptation of the animal to a novel duration.…”

“…To avoid these possibly confounding factors, we used a non-striatum-dependent behavioral measure, the respiratory frequency, to assess the interval timing ability in a Pavlovian fear conditioning associating an odor to a mild footshock. Indeed, the pattern of respiratory frequency has been shown to be a good index temporal expectation of the shock arrival (Boulanger Bertolus et al, 2014;Dupin et al, 2020;Shionoya et al, 2013). This allowed us to look more 4 closely at the role of dorsal striatum and its dopamine level in the initial acquisition of an interval duration, as well as when a change in this duration is applied.…”

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

“…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). This result suggests that an intact dorsal striatum allows the preservation of the temporal behavioral response pattern to the previously learned time interval at the detriment of the shift of the pattern toward the new duration.…”

“…Here, using a nonmotor task -Pavlovian fear conditioning -and assessing the animals' behavioral temporal response through respiration, allowed us to overcome this confound, uncovering a previously undescribed role for the striatum. Our results also concur with previous findings indicating that measuring the respiratory response is relevant to understand the brain activity associated with emotions (Dupin et al, 2019;Moberly et al, 2018), including in the context of interval timing (Dupin et al, 2020). As animals were first conditioned to a 20-s interval duration and then shifted to a 30-s duration, one may wonder whether the respiratory patterns observed for these two durations could reflect non-specific changes in performance with trials repetition instead of temporal adaptation to the new duration.…”

“…To avoid these possibly confounding factors, we used a non-striatum-dependent behavioral measure, the respiratory frequency, to assess the animal's interval timing ability in a Pavlovian fear conditioning associating an odor to a mild footshock. Indeed, the pattern of respiratory frequency has been shown to be a good index of the animal's temporal expectation of the shock arrival (Boulanger Bertolus et al, 2014;Dupin et al, 2020;Shionoya et al, 2013). This allowed us to look more closely at the role of dorsal striatum and its dopamine level in the initial acquisition of an interval duration, as well as when a change in this duration is applied.…”