Subsecond fear discrimination in rats: adult impairment in adolescent heavy alcohol drinkers

DiLeo, Alyssa; Wright, Kristina M; McDannald, Michael A.

doi:10.1101/lm.043257.116

Cited by 19 publications

(34 citation statements)

References 37 publications

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“…As expected, baseline nose poke rates do not differ between trial types. All trial types show the same gradual increase in re- Consistent with our previous results using suppression ratios, measuring rates of nose poking reveals complete discrimination of danger, uncertainty and safey 31,32,39 . Nose poking is reduced to all cues between the first and second sessions, but the emergence of fear discrimination is clearly seen thereafter.…”

Section: Resultssupporting

confidence: 89%

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Foot shock facilitates reward seeking in an experience-dependent manner

Strickland

Dileo

Moaddab

et al. 2020

Preprint

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Animals organize reward seeking around aversive events. An abundance of research shows that foot shock, as well as a shock-associated cue, can elicit freezing and suppress reward seeking. Yet, there is evidence that experience can flip the effect of foot shock to facilitate reward seeking. Here we examine cue suppression, foot shock suppression and foot shock facilitation of reward seeking in a single behavioural setting. Male Long Evans rats received fear discrimination consisting of danger, uncertainty and safety cues. Discrimination took place over a baseline of rewarded nose poking. With limited experience, all cues and foot shock strongly suppressed reward seeking. With continued experience, suppression became specific to shock-associated cues and foot shock facilitated reward seeking. Our results provide a means of assessing positive properties of foot shock, and may provide insight into maladaptive behavior around aversive events.

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Section: Resultssupporting

confidence: 89%

“…Our laboratory has observed robust danger, uncertainty, and safety discrimination using suppression ratios calcluated from rates of rewarded nose poking 31,32,[35][36][37] . Classic studies examining defensive behaviour have reported robust post shock freezing 18,25,38 .…”

Section: Resultsmentioning

confidence: 99%

Foot shock facilitates reward seeking in an experience-dependent manner

Strickland

Dileo

Moaddab

et al. 2020

Preprint

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“…In the procedure, three auditory cues predict unique foot shock probabilities: danger ( p = 1.00), uncertainty ( p = .375) and safety ( p = .00). Using conditioned suppression of rewarded nose poking as our dependent measure, we have previously found excellent discriminative fear in male and female rats: high to danger, intermediate to uncertainty, and low to safety (Berg et al., ; DiLeo, Wright, & McDannald, ; Ray, Hanlon, & McDannald, ; Walker et al., ; Wright et al., ). Theoretically, +PEs provide an updating mechanism that would permit fear to uncertainty to remain at an intermediate level.…”

Section: Resultsmentioning

confidence: 99%

The ventrolateral periaqueductal grey updates fear via positive prediction error

Walker

Wright

Jhou

et al. 2019

Eur J of Neuroscience

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Aversive, positive prediction error (+PE) provides a mechanism to update and increase future fear to uncertain threat predictors. The ventrolateral periaqueductal grey (vlPAG) has been offered as a neural locus for +PE computation. Yet, a causal demonstration of vlPAG +PE activity to update fear remains elusive. We devised a fear discrimination procedure in which a danger cue predicts shock deterministically and an uncertainty cue predicts shock probabilistically, requiring prediction errors to achieve an appropriate fear response. Recording vlPAG single‐unit activity during fear discrimination in Long‐Evans rats, we reveal activity related to shock is consistent with +PE and updates subsequent fear to uncertainty at the trial level. We further demonstrate that vlPAG inhibition during shock selectively decreases future fear to uncertainty, but not danger, and temporal emergence of this effect is consistent with single‐unit activity. These findings provide causal evidence that vlPAG +PE is necessary for fear updating.

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“…Stimuli can be heard or downloaded at http://mcdannaldlab.org/resources/ardbark. Previous studies have found these stimuli to be equally salient, yet highly discriminable (Berg et al, 2014;Wright et al, 2015;DiLeo et al, 2016;Ray et al, 2018). The 42-min pre-exposure sessions consisted of four presentations of each cue (12 total presentations) with a mean inter-trial interval (ITI) of 3.5 min.…”

Section: Pre-exposurementioning

confidence: 99%

“…Drawing from learning theory (Rescorla, 1968), our laboratory has observed rapid scaling of fear to danger, uncertainty and safety in male rats (DiLeo et al, 2016). Present work in our laboratory is aimed at identifying brain regions that permit rapid scaling of fear.…”

Section: Introductionmentioning

confidence: 99%

The nucleus accumbens core is necessary to scale fear to degree of threat

Ray

Russ

Walker

et al. 2020

Preprint

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AbstractFear is adaptive when the level of the response rapidly scales to degree of threat. Using a discrimination procedure consisting of danger, uncertainty and safety cues, we have found rapid fear scaling (within two seconds of cue presentation) in male rats. Here we examined a possible role for the nucleus accumbens core (NAcc) in the acquisition and expression of fear scaling. In experiment 1, male Long Evans rats received bilateral sham or neurotoxic NAcc lesions, recovered and underwent fear discrimination. NAcc-lesioned rats were generally impaired in scaling fear to degree of threat, and specifically impaired in rapid uncertainty-safety discrimination. In experiment 2, male Long Evans rats received NAcc transduction with halorhodopsin or a control fluorophore. After fear scaling was established, the NAcc was illuminated during cue or control periods. NAcc-halorhodopsin rats receiving cue illumination were specifically impaired in rapid uncertainty-safety discrimination. The results reveal a general role for the NAcc in scaling fear to degree of threat, and a specific role in rapid discrimination of uncertain threat and safety.Significance StatementRapidly discriminating cues for threat and safety is essential for survival and impaired threat-safety discrimination is a hallmark of stress and anxiety disorders. In two experiments, we induced nucleus accumbens core (NAcc) dysfunction in rats receiving fear discrimination consisting of cues for danger, uncertainty and safety. Permanent NAcc dysfunction, via neurotoxic lesion, generally disrupted the ability to scale fear to degree of threat, and specifically impaired one component of scaling: rapid discrimination of uncertain threat and safety. Reversible NAcc dysfunction, via optogenetic inhibition, specifically impaired rapid discrimination of uncertain threat and safety. The results reveal that the NAcc is essential to scale fear to degree of threat, and is a plausible source of dysfunction in stress and anxiety disorders.

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Subsecond fear discrimination in rats: adult impairment in adolescent heavy alcohol drinkers

Cited by 19 publications

References 37 publications

Foot shock facilitates reward seeking in an experience-dependent manner

Foot shock facilitates reward seeking in an experience-dependent manner

The ventrolateral periaqueductal grey updates fear via positive prediction error

The nucleus accumbens core is necessary to scale fear to degree of threat

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