A sex-specific role for the bed nucleus of the stria terminalis in proactive defensive behavior

Guerra, Diana P; Wang, Wei; Souza, Karienn A.; Moscarello, Justin M.

doi:10.1038/s41386-023-01581-9

Cited by 10 publications

(4 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The data presented here, in conjunction with a previous report demonstrating that VH suppresses ARs in an alternate shuttle-box context [18], suggest that VH supports dissociable behavioral functions in SAA. VH sends projections to multiple avoidance-relevant brain areas, including the basolateral amygdala [15,26,[52][53][54], nucleus accumbens [16,52,[54][55][56], infralimbic cortex [14,56,57], and the bed nucleus of the stria terminalis [52,58]. Inputs from VH can either stimulate or suppress the activity of principal neurons within the same target region, via direct excitatory connections or feedforward inhibition, respectively [59][60][61][62].…”

Section: Discussionmentioning

confidence: 99%

Ventral hippocampus mediates inter-trial responding in signaled active avoidance

Oleksiak,

Plas,

Carriaga

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

The hippocampus has a central role in regulating contextual processes in memory. We have shown that pharmacological inactivation of ventral hippocampus (VH) attenuates the context-dependence of signaled active avoidance (SAA) in rats. Here, we explore whether the VH mediates intertrial responses (ITRs), which are putative unreinforced avoidance responses that occur between trials. First, we examined whether VH inactivation would affect ITRs. Male rats underwent SAA training and subsequently received intra-VH infusions of saline or muscimol before retrieval tests in the training context. Rats that received muscimol performed significantly fewer ITRs, but equivalent avoidance responses, compared to controls. Next, we asked whether chemogenetic VH activation would increase ITR vigor. In male and female rats expressing excitatory (hM3Dq) DREADDs, systemic CNO administration produced a robust ITR increase that was not due to nonspecific locomotor effects. Then, we examined whether chemogenetic VH activation potentiated ITRs in an alternate (non-training) test context and found it did. Finally, to determine if context-US associations mediate ITRs, we exposed rats to the training context for three days after SAA training to extinguish the context. Rats submitted to context extinction did not show a reliable decrease in ITRs during a retrieval test, suggesting that context-US associations are not responsible for ITRs. Collectively, these results reveal an important role for the VH in context-dependent ITRs during SAA. Further work is required to explore the neural circuits and associative basis for these responses, which may be underlie pathological avoidance that occurs in humans after threat has passed.

show abstract

Section: Discussionmentioning

confidence: 99%

Ventral hippocampus mediates inter-trial responding in signaled active avoidance

Oleksiak,

Plas,

Carriaga

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally, the BNST specifically appears to play a similar role in biasing threat responses towards active coping behaviors, including active struggle bouts during restraint stress, which are associated with increased BNST neural activity (60). Further, chemogenetically inhibition of BNST neurons reduces active avoidance shuttling responses (61). While our data are consistent with the hypothesis that the vagal afferent-to-cNTS A2 -to-vlBNST circuit is necessary for active responses to threat, additional work will be needed to examine the role of gut-sensing vagal afferents and noradrenergic inputs to the vlBNST in active avoidance behavior.…”

Section: Discussionmentioning

confidence: 99%

An ascending vagal sensory-central noradrenergic pathway modulates retrieval of passive avoidance memory

Edwards,

Guerrero,

Thompson

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: Visceral feedback from the body is often subconscious, but plays an important role in guiding motivated behaviors. Vagal sensory neurons relay gut feelings to noradrenergic (NA) neurons in the caudal nucleus of the solitary tract (cNTS), which in turn project to the anterior ventrolateral bed nucleus of the stria terminalis (vlBNST) and other hypothalamic-limbic forebrain regions. Prior work supports a role for these circuits in modulating memory consolidation and extinction, but a potential role in retrieval of conditioned avoidance remains untested. Results: To examine this, adult male rats underwent passive avoidance conditioning. We then lesioned gut-sensing vagal afferents by injecting cholecystokinin-conjugated saporin toxin (CSAP) into the vagal nodose ganglia (Experiment 1), or lesioned NA inputs to the vlBNST by injecting saporin toxin conjugated to an antibody against dopamine-beta hydroxylase (DSAP) into the vlBNST (Experiment 2). When avoidance behavior was later assessed, rats with vagal CSAP lesions or NA DSAP lesions displayed significantly increased conditioned passive avoidance. Conclusions: These new findings support the view that a gut vagal afferent-to-cNTSNA-to-vlBNST circuit plays a role in modulating the expression/retrieval of learned passive avoidance. Overall, our data suggest a dynamic modulatory role of vagal sensory feedback to the limbic forebrain in integrating interoceptive signals with contextual cues that elicit conditioned avoidance behavior.

show abstract

“…In addition, the BNST regulates the impact of stress on aversive learning processes in males, but not females (Bangasser and Shors, 2010), suggesting that it may contribute to stress effects on extinction in male rats reported here. Indeed, chemogenetic activation of BNST in male subjects facilitates the expression of ARs in SAA (Guerra et al, 2023). The BNST is also sexually dimorphic (Allen and Gorski, 1990; Shah et al, 2004; Uchida et al, 2019; Tsukahara and Morishita, 2020), and the action of gonadal steroids and their metabolites in the BNST may play a role in sex-dependent aversive learning processes, such as contextual fear conditioning (Maren et al, 1994; Nagaya et al, 2015; Blair et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Acute stress yields a sex-dependent facilitation of signaled active avoidance in rats

Plas,

Oleksiak,

Pitre

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Post-traumatic stress disorder (PTSD) is a debilitating disorder characterized by excessive fear, hypervigilance, and avoidance of thoughts, situations or reminders of the trauma. Among these symptoms, relatively little is known about the etiology of pathological avoidance. Here we sought to determine whether acute stress influences avoidant behavior in adult male and female rats. We used a stress procedure (unsignaled footshock) that is known to induce long-term sensitization of fear and potentiate aversive learning. Rats were submitted to the stress procedure and, one week later, underwent two-way signaled active avoidance conditioning (SAA). In this task, rats learn to prevent an aversive outcome (shock) by performing a shuttling response when exposed to a warning signal (tone). We found that acute stress significantly enhanced SAA acquisition rate in females, but not males. Female rats exhibited significantly greater avoidance responding on the first day of training relative to controls, reaching similar levels of performance by the second day. Males that underwent the stress procedure showed similar rates of acquisition to controls but exhibited resistance to extinction. This was manifest as both elevated avoidance and intertrial responding across extinction days relative to non-stressed controls, an effect that was not observed in females. In a second experiment, acute stress sensitized footshock unconditioned responses in males, not females. However, males and females exhibited similar levels of stress-enhanced fear learning (SEFL), which was expressed as sensitized freezing to a shock-paired context. Together, these results reveal that acute stress facilitates SAA performance in both male and female rats, though the nature of this effect is different in the two sexes. We did not observe sex differences in SEFL, suggesting that the stress-induced sex difference in performance was selective for instrumental avoidance. Future work will elucidate the neurobiological mechanisms underlying the differential effect of stress on instrumental avoidance in male and female rats.

show abstract

A sex-specific role for the bed nucleus of the stria terminalis in proactive defensive behavior

Cited by 10 publications

References 67 publications

Ventral hippocampus mediates inter-trial responding in signaled active avoidance

Ventral hippocampus mediates inter-trial responding in signaled active avoidance

An ascending vagal sensory-central noradrenergic pathway modulates retrieval of passive avoidance memory

Acute stress yields a sex-dependent facilitation of signaled active avoidance in rats

Contact Info

Product

Resources

About