Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive

Lemos, Julia C.; Wanat, Matthew J.; Smith, Jeffrey S.; Reyes, Beverly A.S.; Hollon, Nick G.; Bockstaele, Elisabeth J. Van; Chavkin, Charles; Phillips, Paul E. M.

doi:10.1038/nature11436

Cited by 281 publications

(295 citation statements)

References 35 publications

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“…Excitingly, recent rodent research has provided a potential pharmacological mechanism by which this modulation may occur (17). In particular, it has been shown that stress switches the role of corticotropin-releasing hormone (CRH) in the striatum from driving corticotropin-releasing factor receptor (CRFR) 1 and CRFR2…”

Section: Discussionmentioning

confidence: 99%

“…SF, safe-fear; SH, safe-happy; TF, threat-fear; TH, threat-happy. receptor-linked appetitive responding to aversive responding, driving "a diametric change in the emotional response to acute stressors" (17). This is particularly relevant because we know that the anxiogenic effects of the translational threat-of-shock paradigm used here are CRH dependent (18).…”

Section: Fig 1 (A)mentioning

confidence: 97%

“…Thus, going forward, elevated striatal aversive PE responses may prove a valuable putative biomarker for anxiety disorders and/or for testing the efficacy of treatments for anxiety (20). Indeed, the rodent study highlighted above suggests the CRH pathways may be promising targets for treating such symptoms (17).…”

Section: Fig 1 (A)mentioning

confidence: 99%

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Stress increases aversive prediction error signal in the ventral striatum

Robinson

Overstreet

Charney

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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From job interviews to the heat of battle, it is evident that people think and learn differently when stressed. In fact, learning under stress may have long-term consequences; stress facilitates aversive conditioning and associations learned during extreme stress may result in debilitating emotional responses in posttraumatic stress disorder. The mechanisms underpinning such stress-related associations, however, are unknown. Computational neuroscience has successfully characterized several mechanisms critical for associative learning under normative conditions. One such mechanism, the detection of a mismatch between expected and observed outcomes within the ventral striatum (i.e., "prediction errors"), is thought to be a critical precursor to the formation of new stimulusoutcome associations. An untested possibility, therefore, is that stress may affect learning via modulation of this mechanism. Here we combine a translational model of stress with a cognitive neuroimaging paradigm to demonstrate that stress significantly increases ventral striatum aversive (but not appetitive) prediction error signal. This provides a unique account of the propensity to form threat-related associations under stress with direct implications for our understanding of both normal stress and stress-related disorders.threat of shock | punishment | anxiety | face perception L earning to associate cues with threat is adaptive because it allows future threat to be predicted and avoided (1). However, such associative learning also may lead to haunting and debilitating memories; the smell of stir-fry may evoke painful intrusive memories in Vietnam veterans. How aversive information is integrated to guide adaptive or maladaptive behavior, however, is not well understood. Here, we report that stress increases a key learning mechanism: the neural detection of a mismatch between an expected and observed aversive outcome within the ventral striatum, commonly referred to as the aversive prediction error (PE) signal (1, 2).Neurocomputational and neuroeconomic accounts of cognition posit that stimulus-outcome associations during conditioning are formed via temporal difference learning (1, 3, 4), in which learning depends upon comparing expectation to what is currently happening. New associations, it is argued, are driven by a difference between predicted and actual outcomes (i.e., "prediction errors"), with greater mismatch between expected and actual outcomes evoking greater PE, resulting in greater predictive learning. This mismatch gives rise to phasic dopamine release in the ventral striatum (1, 3-5) for both appetitive and aversive stimuli (1, 2, 6, 7). Little is known, however, about how PE processing might be affected by an organism's emotional state. Stress, for instance, is well known to facilitate aversive conditioning in both humans and animals (8, 9), raising the possibility that aversive PEs also might be increased by stress. This hypothesis, however, is untested. Therefore, here we used a translational stress induction method in healt...

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Section: Discussionmentioning

confidence: 99%

Section: Fig 1 (A)mentioning

confidence: 97%

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Stress increases aversive prediction error signal in the ventral striatum

Robinson

Overstreet

Charney

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…On the other hand, the effects of GCs on social behavior may depend on the social and environmental context (Orchinik, 1998) as well stressor severity (Lemos et al., 2012). GCs are regarded mainly as permissive or facilitating hormones behind many behaviors, such as self‐grooming or feeding (Katz & Roth, 1979; Packard et al., 2016; Rowland & Antelman, 1976).…”

Section: The Potential Role Of the Stress Axis In Mediating Social Bementioning

confidence: 99%

“…For example, GCs may promote as well as inhibit aggression toward conspecifics depending on social rank, personality and the duration of the stressor (Grace & Anderson, 2014; Summers et al., 2005). Furthermore, while acute HPA‐axis activity may trigger dopamine production, severe stress is known to abolish this rewarding effect and lead to social withdrawal (Lemos et al., 2012). …”

Section: The Potential Role Of the Stress Axis In Mediating Social Bementioning

confidence: 99%

Associations between glucocorticoids and sociality across a continuum of vertebrate social behavior

Raulo

Dantzer

2018

Ecology and Evolution

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The causes and consequences of individual differences in animal behavior and stress physiology are increasingly studied in wild animals, yet the possibility that stress physiology underlies individual variation in social behavior has received less attention. In this review, we bring together these study areas and focus on understanding how the activity of the vertebrate neuroendocrine stress axis (HPA‐axis) may underlie individual differences in social behavior in wild animals. We first describe a continuum of vertebrate social behaviors spanning from initial social tendencies (proactive behavior) to social behavior occurring in reproductive contexts (parental care, sexual pair‐bonding) and lastly to social behavior occurring in nonreproductive contexts (nonsexual bonding, group‐level cooperation). We then perform a qualitative review of existing literature to address the correlative and causal association between measures of HPA‐axis activity (glucocorticoid levels or GCs) and each of these types of social behavior. As expected, elevated HPA‐axis activity can inhibit social behavior associated with initial social tendencies (approaching conspecifics) and reproduction. However, elevated HPA‐axis activity may also enhance more elaborate social behavior outside of reproductive contexts, such as alloparental care behavior. In addition, the effect of GCs on social behavior can depend upon the sociality of the stressor (cause of increase in GCs) and the severity of stress (extent of increase in GCs). Our review shows that the while the associations between stress responses and sociality are diverse, the role of HPA‐axis activity behind social behavior may shift toward more facilitating and less inhibiting in more social species, providing insight into how stress physiology and social systems may co‐evolve.

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New viral‐genetic mapping uncovers an enrichment of corticotropin‐releasing hormone‐expressing neuronal inputs to the nucleus accumbens from stress‐related brain regions

Itoga

Chen

Fateri

et al. 2019

J of Comparative Neurology

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Corticotropin‐releasing hormone (CRH) is an essential, evolutionarily‐conserved stress neuropeptide. In addition to hypothalamus, CRH is expressed in brain regions including amygdala and hippocampus where it plays crucial roles in modulating the function of circuits underlying emotion and cognition. CRH+ fibers are found in nucleus accumbens (NAc), where CRH modulates reward/motivation behaviors. CRH actions in NAc may vary by the individual's stress history, suggesting roles for CRH in neuroplasticity and adaptation of the reward circuitry. However, the origin and extent of CRH+ inputs to NAc are incompletely understood. We employed viral genetic approaches to map both global and CRH+ projection sources to NAc in mice. We injected into NAc variants of a new designer adeno‐associated virus that permits robust retrograde access to NAc‐afferent projection neurons. Cre‐dependent viruses injected into CRH‐Cre mice enabled selective mapping of CRH+ afferents. We employed anterograde AAV1‐directed axonal tracing to verify NAc CRH+ fiber projections and established the identity of genetic reporter‐labeled cells via validated antisera against native CRH. We quantified the relative contribution of CRH+ neurons to total NAc‐directed projections. Combined retrograde and anterograde tracing identified the paraventricular nucleus of the thalamus, bed nucleus of stria terminalis, basolateral amygdala, and medial prefrontal cortex as principal sources of CRH+ projections to NAc. CRH+ NAc afferents were selectively enriched in NAc‐projecting brain regions involved in diverse aspects of the sensing, processing and memory of emotionally salient events. These findings suggest multiple, complex potential roles for the molecularly‐defined, CRH‐dependent circuit in modulation of reward and motivation behaviors.

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Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive

Cited by 281 publications

References 35 publications

Stress increases aversive prediction error signal in the ventral striatum

Stress increases aversive prediction error signal in the ventral striatum

Associations between glucocorticoids and sociality across a continuum of vertebrate social behavior

New viral‐genetic mapping uncovers an enrichment of corticotropin‐releasing hormone‐expressing neuronal inputs to the nucleus accumbens from stress‐related brain regions

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