Role Of Bed Nucleus Of The Stria Terminalis Research Articles

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

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 explore the contribution of BNST to a task in which subjects learn a proactive response that prevents the delivery of an aversive outcome. To this end, male and female rats were trained to shuttle during a tone to avoid shock in a standard two-way signaled active avoidance paradigm. Chemogenetic inhibition (hM4Di) of BNST attenuated the expression of the avoidance response in male but not female rats. Inactivation of the neighboring medial septum in males produced no effect on avoidance, demonstrating that our effect was specific to BNST. A follow up study comparing hM4Di inhibition to hM3Dq activation of BNST in males replicated the effect of inhibition and demonstrated that activation of BNST extended the period of tone-evoked shuttling. These data support the novel conclusion that BNST mediates two-way avoidance behavior in male rats and suggest the intriguing possibility that the systems underlying proactive defensive behavior are sex-specific.

Aberrant functional connectivity of the bed nucleus of the stria terminalis and its age dependence in children and adolescents with social anxiety disorder.

Social anxiety disorder (SAD) is a prevalent and impairing mental disorder among children and adolescents. The bed nucleus of the stria terminalis (BNST) plays a critical role in anxiety disorders, including valence surveillance and hypervigilance for potential threats. However, the role of BNST and its related functional network in children and adolescents with SAD has not been fully investigated. This study examined the aberration of BNST's functional connectivity and its age dependence in adolescents with SAD. Using a sample of 75 SAD patients and 75 healthy controls (HCs) children aged 9-18 years old, we delineated the group-by-age interaction of BNST-seeded functional connectivity (FC) during resting state and movie-watching. The relationships between BNST-seeded FC and clinical scores were also examined. During movie viewing, the FC between the right BNST and the left amygdala, bilateral posterior cingulate cortex (PCC), bilateral superior temporal cortex, and right pericalcarine cortex showed a diagnostic group-by-age interaction. Compared to HCs, SAD patients showed a significant enhancement of the above FC at younger ages. Meanwhile, they showed an age-dependent decrease in FC between the right BNST and left amygdala. Furthermore, for SAD patients, FC between the right BNST and left amygdala during movie viewing was positively correlated with separation anxiety scores. The right BNST plays an essential role in the aberrant brain functioning in children and adolescents with SAD. The atypicality of BNST's FC has remarkable age dependence in SAD, suggesting an association of SAD with neurodevelopmental traits.

Functional Heterogeneity in the Bed Nucleus of the Stria Terminalis.

Early work stressed the differing involvement of the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST) in the genesis of fear versus anxiety, respectively. In 2009, Walker, Miles, and Davis proposed a model of amygdala-BNST interactions to explain these functional differences. This model became extremely influential and now guides a new wave of studies on the role of BNST in humans. Here, we consider evidence for and against this model, in the process highlighting central principles of BNST organization. This analysis leads us to conclude that BNST's influence is not limited to the generation of anxiety-like responses to diffuse threats, but that it also shapes the impact of discrete threatening stimuli. It is likely that BNST-CeA interactions are involved in modulating responses to such threats. In addition, whereas current views emphasize the contributions of the anterolateral BNST region in anxiety, accumulating data indicate that the anteromedial and anteroventral regions also play a critical role. The presence of multiple functional subregions within the small volume of BNST raises significant technical obstacles for functional imaging studies in humans.

The Human BNST: Functional Role in Anxiety and Addiction.

The consequences of chronic stress on brain structure and function are far reaching. Whereas stress can produce short-term adaptive changes in the brain, chronic stress leads to long-term maladaptive changes that increase vulnerability to psychiatric disorders, such as anxiety and addiction. These two disorders are the most prevalent psychiatric disorders in the United States, and are typically chronic, disabling, and highly comorbid. Emerging evidence implicates a tiny brain region-the bed nucleus of the stria terminalis (BNST)-in the body's stress response and in anxiety and addiction. Rodent studies provide compelling evidence that the BNST plays a central role in sustained threat monitoring, a form of adaptive anxiety, and in the withdrawal and relapse stages of addiction; however, little is known about the role of BNST in humans. Here, we review current evidence for BNST function in humans, including evidence for a role in the production of both adaptive and maladaptive anxiety. We also review preliminary evidence of the role of BNST in addiction in humans. Together, these studies provide a foundation of knowledge about the role of BNST in adaptive anxiety and stress-related disorders. Although the field is in its infancy, future investigations of human BNST function have tremendous potential to illuminate mechanisms underlying stress-related disorders and identify novel neural targets for treatment.

The bed nucleus of the stria terminalis is critical for sexual solicitation, but not for opposite-sex odor preference, in female Syrian hamsters

Successful reproduction in vertebrates depends critically upon a suite of precopulatory behaviors that occur prior to mating. In Syrian hamsters (Mesocricetus auratus), these behaviors include vaginal scent marking and preferential investigation of male odors. The neural regulation of vaginal marking and opposite-sex odor preference likely involves an interconnected set of steroid-sensitive nuclei that includes the medial amygdala (MA), the bed nucleus of the stria terminalis (BNST), and the medial preoptic area (MPOA). For example, lesions of MA eliminate opposite-sex odor preference and reduce overall levels of vaginal marking, whereas lesions of MPOA decrease vaginal marking in response to male odors. Although BNST is densely interconnected with both MA and MPOA, little is known about the role of BNST in female precopulatory behaviors. To address this question, females received either bilateral, excitotoxic lesions of BNST (BNST-X) or sham lesions (SHAM), and were tested for scent marking and for investigatory responses to male and female odors. Whereas SHAM females vaginal marked more to male odors than female odors on two days of the estrous cycle, BNST-X females marked at equivalent levels to both odors. This deficit is not due to alterations in social odor investigation, as both BNST-X and SHAM females investigated male odors more than female odors. Finally, BNST lesions did not generally disrupt the cyclic changes in reproductive behaviors that occur across the estrous cycle. Taken together, these results demonstrate that BNST is critical for the normal expression of solicitational behaviors by females in response to male odor stimuli.