Review
Neurosciences
Yana van de Poll, Yasmin Cras, Tommas J. Ellender
Summary: The bed nucleus of the stria terminalis (BNST) is a key region in stress-related psychiatric diseases, with sexual dimorphism and complex structure. It plays a critical role in regulating stress and anxiety behavior and is connected to various brain structures. Understanding its structure and function is crucial for studying human diseases.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Clinical Neurology
Anna Barbara Borges-Assis, Daniela Lescano Uliana, Sara Cristina Hott, Francisco Silveira Guimara, Sabrina Francesca Lisboa, Leonardo Barbosa Moraes Resstel
Summary: The endocannabinoid anandamide (AEA) can decrease the release of neurotransmitters by binding to presynaptic cannabinoid type 1 (CB1) receptors. AEA is hydrolyzed by the enzyme FAAH in the postsynaptic neuron. The present study investigated the role of AEA and CB1 receptors in the Bed Nucleus of the Stria Terminalis (BNST) in modulating anxiety-related behaviors. The findings suggest that eCB signaling in the BNST is recruited during aversive situations to counteract the stress effect.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Olivia B. Levine, Mary Jane Skelly, John D. Miller, Jean K. Rivera-Irizarry, Sydney A. Rowson, Jeffrey F. DiBerto, Jennifer A. Rinker, Todd E. Thiele, Thomas L. Kash, Kristen E. Pleil
Summary: BNST neurons that synthesize CRF play a role in binge alcohol drinking and anxiety, with a sex-dependent PVTVGLUT2-BNSTCRF circuit identified. Chemogenetic inhibition of the PVT-BNST projection promoted binge alcohol drinking only in female mice, while activation reduced avoidance behavior in both sexes. Repeated binge drinking induced a female-like phenotype in the male PVT-BNSTCRF excitatory synapse without altering the function of PVTBNST neurons themselves.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Malini Suresh Nair, Nigel C. Dao, Daniela Lopez Melean, Keith R. Griffith, W. David Starnes, J. Brody Moyer, Avery R. Sicher, Dakota F. Brockway, Kathleen D. Meeks, Nicole A. Crowley
Summary: This study found that somatostatin neurons in the bed nucleus of the stria terminalis (BNST) can reduce binge alcohol consumption in female animals, but not in males. Activation of these neurons did not affect anxiety-like behavior. The findings suggest that somatostatin neurons in the BNST may be a potential target for modulating alcohol use disorder.
BRAIN RESEARCH BULLETIN
(2022)
Article
Behavioral Sciences
William J. Giardino, Matthew B. Pomrenze
Summary: The intricate relationship between sleep, emotional arousal, and neural circuits presents a significant challenge in understanding the impact of sleep quality on emotional responses. Investigating these interrelated factors can provide crucial insights into improving psychiatric treatments and global psychological wellbeing.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Article
Neurosciences
Ke-Wei Zhu, Gui-Jin Tao, Zhi-Li Huang, Wei-Min Qu, Lu Wang
Summary: The bed nucleus of the stria terminalis (BNST) is a neuropeptide-enriched brain region that regulates various emotional behaviors and states. In this study, using virus-based tracing systems, we mapped the inputs and projections of BNST calretinin (CR)-expressing neurons in mice. We found that these neurons primarily received inputs from the amygdalopiriform transition area, central amygdala, and hippocampus. These results provide insights into the neuronal circuits involved in the distinct functions of the BNST.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2023)
Article
Behavioral Sciences
Emi Kikuchi, Tadashi Inui, Shaoyi Su, Yoshiaki Sato, Makoto Funahashi
Summary: Conditioned taste aversion (CTA) is established by pairing a taste solution as a conditioned stimulus (CS) with visceral malaise as an unconditioned stimulus (US). The involvement of the bed nucleus of the stria terminalis (BNST) in CTA and its effects on CS intake were examined through chemogenetic inhibition of BNST neurons.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Neurosciences
Ruotong Li, Yong Wang, Yaxin Yang, Zhongheng Wu, Ling Wang, Guoyi Tang, Jie Yang, Jian Liu
Summary: This study found that GABAA receptor-mediated inhibitory transmission in the avBNST is involved in Parkinson's disease (PD)-related anxiety. Injection of GABAA receptor agonist produced anxiolytic-like effects, inhibited the firing activity of GABAergic neurons and activated the dopaminergic neurons in VTA and serotonergic neurons in DRN, leading to an increase in dopamine and 5-HT release in the amygdala.
Article
Neurosciences
Song-Lin Ding
Summary: The bed nucleus of stria terminalis (BST) is an important structure that mediates sustained vigilant responses. Dysfunction of the BST may lead to excessive anxiety and hypervigilance. This study identifies a new BST subdivision, called BSTsc, which has unique inputs, cell morphology, and molecular signature compared to other BST subdivisions. The BSTsc appears to be a shortcut bridge linking spatial information to internal responses.
JOURNAL OF COMPARATIVE NEUROLOGY
(2022)
Article
Behavioral Sciences
Matthew A. Cooper, Mackenzie K. Hooker, Conner J. Whitten, Jeff R. Kelly, Matthew S. Jenkins, Steve C. Mahometano, Maya C. Scarbrough
Summary: The medial amygdala controls social behavior and regulates responses to stress. Dominant animals showed higher neural activity in BNST-projecting MePD and MePV cells after winning or losing a social encounter. This pathway is associated with both aggression and stress coping responses.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Clinical Neurology
Matilda Naesstrom, Marwan Hariz, Lotta Stromsten, Owe Bodlund, Patric Blomstedt
Summary: DBS in the BNST shows promising clinical outcomes in severe therapy-refractory OCD, with improvements in YBOCS, MADRS, and Global Assessment of Functioning scores. However, further multidisciplinary clinical studies are needed to confirm the efficacy and safety of this treatment.
WORLD NEUROSURGERY
(2021)
Article
Neurosciences
David Hofmann, Thomas Straube
Summary: The study found consistent negative effective connectivity from all amygdala nuclei to the BNST, with weaker and more heterogeneous positive effective connectivity from the BNST to the amygdala. Additionally, there were positive associations between BNST-BNST effective connectivity and anxiety, while CM-BNST effective connectivity showed a negative association with anxiety.
HUMAN BRAIN MAPPING
(2021)
Review
Biochemistry & Molecular Biology
Seong-Rae Kim, Sung-Yon Kim
Summary: Recent investigations have highlighted the key roles of glutamatergic and GABAergic neurons in the bed nucleus of the stria terminalis (BNST) and their axonal projections, showing that these subpopulations oppositely regulate diverse behavioral states. Additionally, studies have revealed unexpected functional specificity and heterogeneity within each subpopulation. More research is needed for a complete understanding of the cellular diversity and functional heterogeneity in the BNST.
MOLECULES AND CELLS
(2021)
Article
Anatomy & Morphology
Brandon M. Sibbach, Helmet T. Karim, Daniel Lo, Nithya Kasibhatla, Tales Santini, Jessica C. Weber, Tamer S. Ibrahim, Layla Banihashemi
Summary: This study used ultra-high field MRI modalities to isolate subregions of the hypothalamus and bed nucleus of the stria terminalis, and generated probabilistic atlases, providing resources for further research on stress-related function and psychopathology.
BRAIN STRUCTURE & FUNCTION
(2023)
Article
Cell Biology
Juanjuan Zhao, Chengyu Liu, Fenyan Zhang, Ziyi Zheng, Fenlan Luo, Jianxia Xia, Yaling Wang, Zehui Zhang, Jinxiang Tang, Zhenbo Song, Siyu Li, Kan Xu, Mengting Chen, Chenggang Jiang, Chao He, Ling Tang, Zhian Hu, Dong Gao, Shuancheng Ren
Summary: The neural circuit of the paraventricular thalamus (PVT) plays a crucial role in controlling wakefulness under stress conditions. Research has found that PVT neurons projecting to the central amygdala (CeA) are activated by different stressors and are active during wakefulness. Activation of the PVT-CeA circuit can induce transitions from sleep to wakefulness, while inhibition of this circuit decreases wakefulness.
Article
Biochemistry & Molecular Biology
Megan E. Fox, Ramesh Chandra, Miriam S. Menken, Emily J. Larkin, Hyungwoo Nam, Michel Engeln, T. Chase Francis, Mary Kay Lobo
MOLECULAR PSYCHIATRY
(2020)
Article
Biochemistry & Molecular Biology
Jason B. Alipio, Adam T. Brockett, Megan E. Fox, Stephen S. Tennyson, Coreylyn A. deBettencourt, Dina El-Metwally, Nikolas A. Francis, Patrick O. Kanold, Mary Kay Lobo, Matthew R. Roesch, Asaf Keller
Summary: This study found that perinatal exposure to fentanyl in mice resulted in withdrawal behavior and behavioral abnormalities in early adulthood, similar to humans born with NOWS. These effects were seen in terms of changes in behavior and physiology that normalized as the mice reached adulthood.
Article
Biochemistry & Molecular Biology
Michel Engeln, Yang Song, Ramesh Chandra, Ashley La, Megan E. Fox, Brianna Evans, Makeda D. Turner, Shavin Thomas, T. Chase Francis, Ronna Hertzano, Mary Kay Lobo
Summary: The study suggests that motor stereotypies in early-onset neuropsychiatric diseases may be associated with dysregulated basal ganglia direct-pathway activity, with neurobiological mechanisms leading to direct-pathway neuron disconnectivity in stereotypy remaining poorly understood. The research uncovers phenotype-specific molecular alterations in D1-MSNs associated with morphological adaptations in mice displaying stereotypy behavior.
MOLECULAR PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Megan E. Fox, Antonio Figueiredo, Miriam S. Menken, Mary Kay Lobo
SCIENTIFIC REPORTS
(2020)
Article
Neurosciences
Michel Engeln, Megan E. Fox, Mary Kay Lobo
Summary: Stress exposure has a lasting impact on motivated behavior and drug reward, often shaping drug-related behaviors bidirectionally. Social housing conditions can influence cocaine-related behaviors after psychosocial stress, with pair-housed mice showing increased social avoidance after CSDS and decreased cocaine intake. Single-housed mice, on the other hand, exhibit stress-sensitive cocaine intake and increased social avoidance after CSDS.
PSYCHOPHARMACOLOGY
(2021)
Article
Behavioral Sciences
Olivia Uddin, Carleigh Jenne, Megan E. Fox, Keiko Arakawa, Asaf Keller, Nathan Cramer
Summary: Research on rats and mice showed that they differ in experiencing withdrawal and pain, with rats more likely to express ongoing pain and mice exhibiting thermal hyperalgesia. These species differences highlight strengths as model systems and can guide experimental design in opioid withdrawal studies.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2021)
Article
Neurosciences
Jason B. Alipio, Catherine Haga, Megan E. Fox, Keiko Arakawa, Rakshita Balaji, Nathan Cramer, Mary Kay Lobo, Asaf Keller
Summary: The study reveals that perinatal fentanyl exposure has lasting consequences on sensory processing and function in mice, impacting their somatosensory function and behavior extending at least to adolescence. This exposure leads to abnormal changes in synaptic excitation, morphological structure, and mRNA expression in the brains of the exposed mice.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Behavioral Sciences
Daniela Franco, Andreas B. Wulff, Mary Kay Lobo, Megan E. Fox
Summary: Chronic stress may increase the risk of developing substance use disorders in vulnerable individuals. This study found that the consumption of fentanyl, a substance commonly used for pain management, was influenced by chronic psychosocial stress in mice, with sex and behavioral outcomes to stress playing a significant role.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Article
Psychiatry
Cali A. Calarco, Megan E. Fox, Saskia Van Terheyden, Makeda D. Turner, Jason B. Alipio, Ramesh Chandra, Mary Kay Lobo
Summary: The widespread use of fentanyl and in utero exposure to the drug can impact mitochondrial function, leading to altered reward-related behavior in adolescence. Gender also plays a role in the effects of developmental fentanyl exposure on mitochondrial function and behavior.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Psychiatry
Marco Pagliusi, Daniela Franco, Shannon Cole, Gessynger Morais-Silva, Ramesh Chandra, Megan E. Fox, Sergio D. Iniguez, Cesar R. Sartori, Mary Kay Lobo
Summary: Brain-derived neurotrophic factor (BDNF) plays a critical role in stress response, exerting different plasticity effects through its receptors (TrkB and TrkB.t1). The study found that BDNF has an anti-stress effect in the hippocampus and a stress-susceptible effect in the nucleus accumbens (NAc). Furthermore, overexpression of TrkB.t1 in specific projection neurons (D2-MSNs) in the NAc can prevent stress-induced social avoidance behavior.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Michel Engeln, Megan E. Fox, Ramesh Chandra, Eric Y. Choi, Hyungwoo Nam, Houman Qadir, Shavin S. Thomas, Victoria M. Rhodes, Makeda D. Turner, Rae J. Herman, Cali A. Calarco, Mary Kay Lobo
Summary: The study identified the transcriptional mechanisms occurring in the VP following drug exposure and the important role of Nr4a1 in cocaine-related behaviors. Overexpression of Nr4a1 enhanced drug-seeking and drug-induced reinstatement, while Nr4a1 knockdown prevented self-administration acquisition and subsequent cocaine-mediated behaviors, highlighting the crucial role of the VP -> MDT circuit in drug intake and relapse-like behaviors.
MOLECULAR PSYCHIATRY
(2022)
Article
Neurosciences
Megan E. Fox, Andreas B. Wulff, Daniela Franco, Eric Y. Choi, Cali A. Calarco, Michel Engeln, Makeda D. Turner, Ramesh Chandra, Victoria M. Rhodes, Scott M. Thompson, Seth A. Ament, Mary Kay Lobo
Summary: Opioid discontinuation leads to withdrawal symptoms and increased negative affect. The neural mechanisms underlying these symptoms, especially in relation to synthetic opioids, are not fully understood.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Neurosciences
Gessynger Morais-Silva, Rianne R. Campbell, Hyungwoo Nam, Mahashweta Basu, Marco Pagliusi, Megan E. Fox, C. Savio Chan, Sergio D. Iniguez, Seth Ament, Nathan Cramer, Marcelo Tadeu Marin, Mary Kay Lobo
Summary: The altered activity of the ventral pallidum (VP) is responsible for disrupted motivation in stress and drug exposure. To investigate the role of Neuronal PAS 1-positive (Npas1+) VP neurons, we analyzed their projection targets and conducted RNA sequencing on VP Npas1+ neurons to understand their molecular identities. Chemogenetic activation of VP Npas1+ neurons modulated susceptibility to social stressors and anxiety-like behavior. Our findings reveal the circuitry, molecular identity, and stress response role of VP Npas1+ neurons.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Jimmy Olusakin, Gautam Kumar, Mahashweta Basu, Cali A. Calarco, Megan E. Fox, Jason B. Alipio, Catherine Haga, Makeda D. Turner, Asaf Keller, Seth A. Ament, Mary Kay Lobo
Summary: The use of fentanyl has significantly increased in the past decade, including among women of reproductive ages. Perinatal exposure to opioids, such as fentanyl, has been associated with adverse neonatal outcomes and long-term behavioral disruptions. This study investigated the molecular adaptations in various brain regions of perinatal fentanyl exposed mice, revealing distinct transcriptomes and differential gene expression between sexes.
NEUROPSYCHOPHARMACOLOGY
(2023)
Meeting Abstract
Neurosciences
Olivier George
NEUROPSYCHOPHARMACOLOGY
(2020)