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

Abstract

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.

50 Years of Research on Dopamine’s Role in Passive Aversive Conditioning and Extinction: A Systematic Review

“…Later research suggested that DA release may be restricted to the shell as opposed to the core (Martinez et al, 2008;Pezze et al, 2001;. Yet, other in-vivo microdialysis studies found that during fear acquisition and recall, DA levels decreased in the whole striatum and dorsal striatum but did not change in the dorsolateral striatum (Boulanger-Bertolus et al, 2021;Katoh et al, 1996;Matsumoto et al, 2005).…”

“…[Insert figure 1 1997; Lane et al, 1982;Morrow et al, 1995;Tsuchiya et al, 1996a) levels of DA and its metabolites (DOPAC or HVA) from ex-vivo whole striatum, dorsal striatum and nucleus accumbens. Most but not all in-vivo microdialysis studies reported DA release in the nucleus accumbens during fear acquisition, recall, and extinction acquisition (Boulanger-Bertolus et al, 2021;Fulford et al, 2007;Kawade et al, 2023;Wilkinson et al, 1998;Young et al, 1993;Young, 2004). Later research suggested that DA release may be restricted to the shell as opposed to the core (Martinez et al, 2008;Pezze et al, 2001;.…”

65 years of research on dopamine's role in classical fear conditioning and extinction: A systematic review

“…Most, but not all, rat studies using in vivo microdialysis reported DA release in the nucleus accumbens during fear acquisition, recall and extinction training (Boulanger-Bertolus et al, 2021;Fulford & Marsden, 2007;Kawade et al, 2022;Wilkinson et al, 1998;Young et al, 1993;Young, 2004), and this release may differ in the accumbal shell versus the core (Martinez et al, 2008;Pezze et al, 2001Pezze et al, , 2002. Yet, others have reported decreased or unaltered DA microdialysis measurements in the whole striatum and dorsal striatum (Boulanger-Bertolus et al, 2021;Katoh et al, 1996;Matsumoto et al, 2005) (Table S5).…”