Activation of corticotropin releasing factor-containing neurons in the rat central amygdala and bed nucleus of the stria terminalis following exposure to two different anxiogenic stressors

Butler, Ryan K.; Oliver, Elisabeth M.; Sharko, Amanda C.; Parilla-Carrero, Jeffrey; Kaigler, Kris F.; Fadel, Jim R.; Wilson, Marlene A.

doi:10.1016/j.bbr.2016.01.051

Cited by 45 publications

(28 citation statements)

References 54 publications

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“…BNST CRH signaling plays a pivotal role in stress-induced anxiety disorders (Choi et al, 2006;Tran et al, 2014;Butler et al, 2016;Donner et al, 2020). However, the precise mechanisms underlying how chronic stress induces BNST CRH neuronal dysfunction were unclear.…”

Section: Discussionmentioning

confidence: 99%

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Chronic Stress Induces Maladaptive Behaviors by Activating Corticotropin-Releasing Hormone Signaling in the Mouse Oval Bed Nucleus of the Stria Terminalis

Liu

Maita

et al. 2020

J. Neurosci.

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The bed nucleus of the stria terminalis (BNST) is a forebrain region highly responsive to stress that expresses corticotropin-releasing hormone (CRH) and is implicated in mood disorders, such as anxiety. However, the exact mechanism by which chronic stress induces CRH-mediated dysfunction in BNST and maladaptive behaviors remains unclear. Here, we first confirmed that selective acute optogenetic activation of the oval nucleus BNST (ovBNST) increases maladaptive avoidance behaviors in male mice. Next, we found that a 6 week chronic variable mild stress (CVMS) paradigm resulted in maladaptive behaviors and increased cellular excitability of ovBNST CRH neurons by potentiating mEPSC amplitude, altering the resting membrane potential, and diminishing M-currents (a voltage-gated K ϩ current that stabilizes membrane potential) in ex vivo slices. CVMS also increased c-fos ϩ cells in ovBNST following handling. We next investigated potential molecular mechanism underlying the electrophysiological effects and observed that CVMS increased CRH ϩ and pituitary adenylate cyclase-activating polypeptide ϩ (PACAP; a CRH upstream regulator) cells but decreased striatal-enriched protein tyrosine phosphatase ϩ (a STEP CRH inhibitor) cells in ovBNST. Interestingly, the electrophysiological effects of CVMS were reversed by CRHR1-selective antagonist R121919 application. CVMS also activated protein kinase A (PKA) in BNST, and chronic infusion of the PKA-selective antagonist H89 into ovBNST reversed the effects of CVMS. Coadministration of the PKA agonist forskolin prevented the beneficial effects of R121919. Finally, CVMS induced an increase in surface expression of phosphorylated GluR1 (S845) in BNST. Collectively, these findings highlight a novel and indispensable stress-induced role for PKA-dependent CRHR1 signaling in activating BNST CRH neurons and mediating maladaptive behaviors.

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Section: Discussionmentioning

confidence: 99%

“…CRH signaling is linked to negative affective states in BNST (Davis et al, 1997;Lee and Davis, 1997;Koob and Heinrichs, 1999;Sahuque et al, 2006;Butler et al, 2016;Faria et al, 2016). Notably, local CRH signaling in ovBNST (which harbors the highest CRH concentration in BNST) is stress responsive (Dabrowska et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Chronic Stress Induces Maladaptive Behaviors by Activating Corticotropin-Releasing Hormone Signaling in the Mouse Oval Bed Nucleus of the Stria Terminalis

Liu

Maita

et al. 2020

J. Neurosci.

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“…Currently, it is understood that BNST neurons do not react uniformly to these various stressful stimuli. For example, the BNST has been shown to exhibit alterations (albeit, increases or decreases depending on the study) in immediate early gene expression in its anterolateral and anteroventral regions after restraint alone, inescapable tailshock, or predator odor (Lino- de-Oliveira et al 2001;Day et al 2005;Christianson et al 2011;Butler et al 2016). Electrophysiological studies have further shown that aversive footshock exposure can rapidly recruit and modify activity in BNST neurons (Marcinkiewcz et al 2016; also, see Daldrup et al 2016).…”

Section: Bnst Function In Response To Unconditioned Aversive Stimulimentioning

confidence: 99%

Role of the bed nucleus of the stria terminalis in aversive learning and memory

Goode

2017

Learn. Mem.

115

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Surviving threats in the environment requires brain circuits for detecting (or anticipating) danger and for coordinating appropriate defensive responses (e.g., increased cardiac output, stress hormone release, and freezing behavior). The bed nucleus of the stria terminalis (BNST) is a critical interface between the "affective forebrain"-including the amygdala, ventral hippocampus, and medial prefrontal cortex-and the hypothalamic and brainstem areas that have been implicated in neuroendocrine, autonomic, and behavioral responses to actual or anticipated threats. However, the precise contribution of the BNST to defensive behavior is unclear, both in terms of the antecedent stimuli that mobilize BNST activity and the consequent defensive reactions. For example, it is well known that the BNST is essential for contextual fear conditioning, but dispensable for fear conditioning to discrete conditioned stimuli (CSs), at least as indexed by freezing behavior. However, recent evidence suggests that there are circumstances in which contextual freezing may persist independent of the BNST. Furthermore, the BNST is involved in the reinstatement (or relapse) of conditioned freezing to extinguished discrete CSs. As such, there are critical gaps in understanding how the BNST contributes to fundamental processes involved in Pavlovian fear conditioning. Here, we attempt to provide an integrative account of BNST function in fear conditioning. We discuss distinctions between unconditioned stress and conditioned fear and the role of BNST circuits in organizing behaviors associated with these states. We propose that the BNST mediates conditioned defensive responses-not based on the modality or duration of the antecedent threat or the duration of the behavioral response to the threat-but rather as consequence the ability of an antecedent stimulus to predict when an aversive outcome will occur (i.e., its temporal predictability). We argue that the BNST is not uniquely mobilized by sustained threats or uniquely involved in organizing sustained fear responses. In contrast, we argue that the BNST is involved in organizing fear responses to stimuli that poorly predict danger will occur, no matter the duration, modality, or complexity of those stimuli. The concepts discussed in this review are critical to understanding the contribution of the human BNST to fear and anxiety disorders.

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“…Interestingly, CRF suppresses feeding when administered in the brain and CRF signaling mediates the anorexigenic effect of several stressors (see [62] for review). While CeA CRF neurons can be recruited by stress ( [63,64], but see [65]), our findings indicate that their activity is not sufficient to inhibit feeding.…”

Section: Discussionmentioning

confidence: 73%

Chemogenetic stimulation of mouse central amygdala corticotropin-releasing factor neurons: Effects on cellular and behavioral correlates of alcohol dependence

Kreifeldt

Herman

Sidhu

et al. 2020

Preprint

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Background. Corticotropin-releasing factor (CRF) signaling in the central nucleus of the amygdala (CeA) plays a critical role in rodent models of excessive alcohol drinking.However, the source of CRF acting in the CeA during alcohol withdrawal remains to be identified. In the present study, we hypothesized that CeA CRF interneurons may represent a behaviorally relevant source of CRF to the CeA increasing motivation for alcohol via negative reinforcement.Methods. We tested this hypothesis in male mice and used chemogenetics to stimulate CeA CRF neurons in vitro and in vivo.Results. We first observed that Crh mRNA expression in the anterior part of the mouse CeA, at the junction with the interstitial nucleus of the posterior limb of the anterior commissure, correlates positively with alcohol intake in C57BL/6J males with a history of chronic binge drinking. We then found that chemogenetic activation of CeA CRF neurons in Crh-IRES-Cre mouse brain slices increases gamma-aminobutyric acid (GABA) release in the medial CeA in part via CRF1 receptor activation, indicating local CRF release. While chemogenetic stimulation of CeA CRF neurons exacerbated novelty-induced feeding suppression, as seen in C57BL/6J males withdrawn from chronic intermittent alcohol inhalation, it had no effect on voluntary alcohol consumption, following either acute or chronic manipulation.Conclusions. Altogether, these findings indicate that hyperactivity of CeA CRF neurons may contribute to elevated CeA GABA levels and negative affect during alcohol withdrawal but is not sufficient to drive alcohol intake escalation in dependent mice. amygdala (CeA) during alcohol withdrawal [12] and blockade of CRF1 signaling in the CeA reduces the anxiogenic-like effect of alcohol withdrawal [13,14], dependenceinduced increases in alcohol self-administration [15, 16], as well as heavy binge drinking [17]. CRF1 in the CeA also mediates the elevation of gamma-aminobutyric acid (GABA) 4 dialysate induced by alcohol dependence [18] and CRF1 overexpression in the CeA potentiates stress-induced reinstatement of alcohol seeking [19].Despite this wealth of converging evidence, the specific neurons responsible for the release of CRF in the CeA during alcohol withdrawal have not been identified. In the present study, we tested the hypothesis that these neurons are intrinsic to the CeA. This hypothesis was supported by evidence that Crh is upregulated in the CeA of alcoholdependent and post-dependent rats [18,20,21], along with our own findings (reported here) that Crh expression in the anterior part of the CeA correlates with alcohol intake in mice with a history of chronic alcohol drinking followed by abstinence. Importantly, psychological stress also upregulates Crh in the CeA [22][23][24] and CRF synthesis in the CeA plays a critical role in mediating anxiety-like behavior [25, 26]. In addition, CRF1expressing neurons in the CeA receive direct input from local interneurons [27] and CeA CRF neurons provide both local inhibitory GABA and excitatory CRF1-mediated sign...

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Activation of corticotropin releasing factor-containing neurons in the rat central amygdala and bed nucleus of the stria terminalis following exposure to two different anxiogenic stressors

Cited by 45 publications

References 54 publications

Chronic Stress Induces Maladaptive Behaviors by Activating Corticotropin-Releasing Hormone Signaling in the Mouse Oval Bed Nucleus of the Stria Terminalis

Chronic Stress Induces Maladaptive Behaviors by Activating Corticotropin-Releasing Hormone Signaling in the Mouse Oval Bed Nucleus of the Stria Terminalis

Role of the bed nucleus of the stria terminalis in aversive learning and memory

Chemogenetic stimulation of mouse central amygdala corticotropin-releasing factor neurons: Effects on cellular and behavioral correlates of alcohol dependence

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