Aerobic exercise after extinction learning reduces return of fear and enhances memory of items encoded during extinction learning

Crombie, Kevin M.; Azar, Ameera; Botsford, Chloe; Heilicher, Mickela; Moughrabi, Nicole; Gruichich, Tijana Sagorac; Schomaker, Chloe M.; Dunsmoor, Joseph E.; Cisler, Josh M.

doi:10.1016/j.mhpa.2023.100510

Cited by 8 publications

(1 citation statement)

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“…Female rats exposed to fear extinction training during estrous phases characterized by high levels of ovarian hormones (proestrus and estrus) do not display fear renewal [40], and stimulus-evoked DA release in the DLS is greater in female rats during these phases [56]. Additionally, a bout of physical activity during the acquisition or consolidation of fear extinction reduces fear renewal in both rodents [39,40,57] and humans [58][59][60]. Physical activity sensitizes DA release in the DLS [61] and potentiates stress-evoked activity of DLS D1R-expressing neurons [62].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological manipulations of the dorsomedial and dorsolateral striatum during fear extinction have opposing effects on fear renewal

Tanner,

Hohorst,

Westerman

et al. 2024

Preprint

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Systemic manipulations that enhance dopamine (DA) transmission around the time of fear extinction can strengthen fear extinction and reduce conditioned fear relapse. Prior studies investigating the brain regions where DA augments fear extinction focus on targets of mesolimbic and mesocortical DA systems originating in the ventral tegmental area, given the role of these DA neurons in prediction error. The dorsal striatum (DS), a primary target of the nigrostriatal DA system originating in the substantia nigra (SN), is implicated in behaviors beyond its canonical role in movement, such as reward and punishment, goal-directed action, and stimulus-response associations, but whether DS DA contributes to fear extinction is unknown. We have observed that chemogenetic stimulation of SN DA neurons during fear extinction prevents the return of fear in contexts different from the extinction context, a form of relapse called renewal. This effect of SN DA stimulation is mimicked by a DA D1 receptor (D1R) agonist injected into the DS, thus implicating DS DA in fear extinction. Different DS subregions subserve unique functions of the DS, but it is unclear where in the DS D1R agonist acts during fear extinction to reduce renewal. Furthermore, although fear extinction increases neural activity in DS subregions, whether neural activity in DS subregions is causally involved in fear extinction is unknown. To explore the role of DS subregions in fear extinction, adult, male Long-Evans rats received microinjections of either the D1R agonist SKF38393 or a cocktail consisting of GABAA/GABAB receptor agonists muscimol/baclofen selectively into either dorsomedial (DMS) or dorsolateral (DLS) DS subregions immediately prior to fear extinction, and extinction retention and renewal were subsequently assessed drug-free. While increasing D1R signaling in the DMS during fear extinction did not impact fear extinction retention or renewal, DMS inactivation reduced later renewal. In contrast, DLS inactivation had no effect on fear extinction retention or renewal but increasing D1R signaling in the DLS during extinction reduced fear renewal. These data suggest that DMS and DLS activity during fear extinction can have opposing effects on later fear renewal, with the DMS promoting renewal and the DLS opposing renewal. Mechanisms through which the DS could influence the contextual gating of fear extinction are discussed.

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