Neurochemically distinct populations of the bed nucleus of stria terminalis modulate innate fear response to weak threat evoked by predator odor stimuli

Bruzsik, Biborka; Biró, László Péter; Sarosdi, Klara Rebeka; Zelena, Dóra; Sipos, Eszter; Szebik, Huba; Török, Bibiána; Mikics, Éva; Tóth, Máté

doi:10.1016/j.ynstr.2021.100415

Cited by 21 publications

(20 citation statements)

References 69 publications

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“…These heterogeneous behavioral functions are reflected in the anatomical heterogeneity of the BNST, which a collection of small, complexly interconnected sub-nuclei comprised of multiple cell types 38-41 . Distinct populations within specific BNST sub-nuclei have already been shown to underpin specific defensive responses 42-45 , suggesting that contrasting proactive and reactive behavioral functions may indeed be supported by dissociable mechanisms within BNST, similar to what meticulous circuit-dissection work has revealed of a related structure, the central amygdala 46-49 . Future research will parse the circuits underlying heterogenous repertoire of BNST-dependent defensive behavior.…”

Section: Discussionmentioning

confidence: 82%

The bed nucleus of the stria terminalis mediates the expression of proactive defensive behavior

Guerra

Wang

Souza

et al. 2022

Preprint

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The bed nucleus of the stria terminalis (BNST) is a forebrain region implicated in aversive responses to uncertain threat. Much of the work on the role of BNST in defensive behavior has used Pavlovian paradigms in which the subject reacts to aversive stimuli delivered in a pattern determined entirely by the experimenter. Here, we report that BNST also mediates proactive defensive responses in a task that allows subjects to prevent the delivery of an aversive outcome. In a standard two-way signaled active avoidance paradigm, male rats learned to shuttle during a tone to avoid shock. Our data demonstrate that chemogenetic inhibition (hM4Di) of BNST attenuates the expression of the avoidance response, whereas chemogenetic activation (hM3Dq) of BNST potentiates the response by extending the period of tone-evoked shuttling. This effect was specific to the BNST, as inactivation of the neighboring medial septum produced no effect on the expression of avoidance. These data support the novel conclusion that BNST mediates two-way avoidance behavior in male rats.

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Section: Discussionmentioning

confidence: 82%

The bed nucleus of the stria terminalis mediates the expression of proactive defensive behavior

Guerra

Wang

Souza

et al. 2022

Preprint

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“…However, we found a significant anxiogenic effect of OVX in EPM only, the most frequently used anxiety test ( 64 , 104 ). On the contrary, an AD effect was visible in the FOT test measuring innate fear and anxiety-related behavior ( 75 ). We found that 3xTg-AD animals spend more time freezing, which suggests that these animals were more frightened ( 75 , 105 ).…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, an AD effect was visible in the FOT test measuring innate fear and anxiety-related behavior ( 75 ). We found that 3xTg-AD animals spend more time freezing, which suggests that these animals were more frightened ( 75 , 105 ). Also, 3xTg-AD animals spend less time exploring and rearing, which might reflect anxiety, too (see immobility in CFT) ( 106 ).…”

Section: Discussionmentioning

confidence: 99%

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Ovariectomy-induced hormone deprivation aggravates Aβ1-42 deposition in the basolateral amygdala and cholinergic fiber loss in the cortex but not cognitive behavioral symptoms in a triple transgenic mouse model of Alzheimer’s disease

et al. 2022

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Alzheimer’s disease is the most common type of dementia, being highly prevalent in elderly women. The advanced progression may be due to decreased hormone synthesis during post-menopause as estradiol and progesterone both have neuroprotective potentials. We aimed to confirm that female hormone depletion aggravates the progression of dementia in a triple transgenic mouse model of Alzheimer’s disease (3xTg-AD). As pathological hallmarks are known to appear in 6-month-old animals, we expected to see disease-like changes in the 4-month-old 3xTg-AD mice only after hormone depletion. Three-month-old female 3xTg-AD mice were compared with their age-matched controls. As a menopause model, ovaries were removed (OVX or Sham surgery). After 1-month recovery, the body composition of the animals was measured by an MRI scan. The cognitive and anxiety parameters were evaluated by different behavioral tests, modeling different aspects (Y-maze, Morris water maze, open-field, social discrimination, elevated plus maze, light–dark box, fox odor, operant conditioning, and conditioned fear test). At the end of the experiment, uterus was collected, amyloid-β accumulation, and the cholinergic system in the brain was examined by immunohistochemistry. The uterus weight decreased, and the body weight increased significantly in the OVX animals. The MRI data showed that the body weight change can be due to fat accumulation. Moreover, OVX increased anxiety in control, but decreased in 3xTg-AD animals, the later genotype being more anxious by default based on the anxiety z-score. In general, 3xTg-AD mice moved less. In relation to cognition, neither the 3xTg-AD genotype nor OVX surgery impaired learning and memory in general. Despite no progression of dementia-like behavior after OVX, at the histological level, OVX aggravated the amyloid-β plaque deposition in the basolateral amygdala and induced early cholinergic neuronal fiber loss in the somatosensory cortex of the transgenic animals. We confirmed that OVX induced menopausal symptoms. Removal of the sexual steroids aggravated the appearance of AD-related alterations in the brain without significantly affecting the behavior. Thus, the OVX in young, 3-month-old 3xTg-AD mice might be a suitable model for testing the effect of new treatment options on structural changes; however, to reveal any beneficial effect on behavior, a later time point might be needed.

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“…In addition, the BST appears to play a role in conditioned fear responses with a temporal aspect ( Goode and Maren, 2017 ). Moreover, recent studies suggest that the BST modulates the response to weak, uncertain threats ( Glover et al, 2020 ; Bruzsik et al, 2021 ).…”

Section: The Mechanisms Of Odor-induced Stress Reactions: Olfaction A...mentioning

confidence: 99%

The Anterior Piriform Cortex and Predator Odor Responses: Modulation by Inhibitory Circuits

Matsukawa

Yoshikawa

Katsuyama

et al. 2022

Front. Behav. Neurosci.

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Rodents acquire more information from the sense of smell than humans because they have a nearly fourfold greater variety of olfactory receptors. They use olfactory information not only for obtaining food, but also for detecting environmental dangers. Predator-derived odor compounds provoke instinctive fear and stress reactions in animals. Inbred lines of experimental animals react in an innate stereotypical manner to predators even without prior exposure. Predator odors have also been used in models of various neuropsychiatric disorders, including post-traumatic stress disorder following a life-threatening event. Although several brain regions have been reported to be involved in predator odor-induced stress responses, in this mini review, we focus on the functional role of inhibitory neural circuits, especially in the anterior piriform cortex (APC). We also discuss the changes in these neural circuits following innate reactions to odor exposure. Furthermore, based on the three types of modulation of the stress response observed by our group using the synthetic fox odorant 2,5-dihydro-2,4,5-trimethylthiazoline, we describe how the APC interacts with other brain regions to regulate the stress response. Finally, we discuss the potential therapeutic application of odors in the treatment of stress-related disorders. A clearer understanding of the odor–stress response is needed to allow targeted modulation of the monoaminergic system and of the intracerebral inhibitory networks. It would be improved the quality of life of those who have stress-related conditions.

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Neurochemically distinct populations of the bed nucleus of stria terminalis modulate innate fear response to weak threat evoked by predator odor stimuli

Cited by 21 publications

References 69 publications

The bed nucleus of the stria terminalis mediates the expression of proactive defensive behavior

The bed nucleus of the stria terminalis mediates the expression of proactive defensive behavior

Ovariectomy-induced hormone deprivation aggravates Aβ1-42 deposition in the basolateral amygdala and cholinergic fiber loss in the cortex but not cognitive behavioral symptoms in a triple transgenic mouse model of Alzheimer’s disease

The Anterior Piriform Cortex and Predator Odor Responses: Modulation by Inhibitory Circuits

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