Somatostatin neurons in the bed nucleus of the stria terminalis play a sex-dependent role in binge Drinking

Nair, Malini Suresh; Dao, Nigel C.; Melean, Daniela Lopez; Griffith, Keith R; Starnes, William D.; Moyer, J. Brody; Sicher, Avery; Brockway, Dakota F.; Meeks, Kathleen D.; Crowley, Nicole A.

doi:10.1016/j.brainresbull.2022.05.010

Cited by 11 publications

(8 citation statements)

References 47 publications

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“…DID was conducted as previously published (Dao et al, 2021; Rhodes et al, 2005; Suresh Nair et al, 2022), at timepoints adapted for adolescence (Holstein et al, 2011; Dao et al, 2020) Mice received 20% (v/v) ethanol (EtOH; Koptec, Decon Labs, King of Prussia, PA) in tap water beginning 3 hr into the dark cycle, for 2 hr (i.e., 10:00 am to 12:00 pm) on three consecutive days. On the fourth day, EtOH was presented for 4 hr (i.e., 10:00 am to 2:00 pm), representing the “binge” day.…”

Section: Methodsmentioning

confidence: 99%

“…SST+ cell counts in SST-IRES-Cre:Ai9 mice, expressing the fluorophore tdTomato exclusively in SST-expressing neurons, were quantified using ImageJ (National Institutes of Health, Bethesda, MD, United States). The PL cortex was delineated and SST+ were automatically quantified under matched criteria for size, circularity, and intensity consistently with our previously published work (Dao et al, 2020;Suresh Nair et al, 2022). The threshold to highlight SST+ cells counted was set at 8.10±.01.…”

Section: Histology and Sst Cell Countsmentioning

confidence: 99%

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Adolescent binge drinking leads to long-lasting changes in cortical microcircuits in mice

Sicher

Starnes

Griffith

et al. 2022

Preprint

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Adolescent drug consumption has increased risks to the individual compared to consumption in adulthood, due to the likelihood of long-term and permanent behavioral and neurological adaptations. However, little is known about how adolescent alcohol consumption influences the maturation and trajectory of cortical circuit development. Here, we explore the consequences of adolescent binge drinking on somatostatin (SST) neuronal function in the prelimbic (PL) cortex. We find that adolescent drinking-in-the-dark (DID) produces sex-dependent increases in intrinsic excitability of SST neurons, persisting well into adulthood. We found a complementary reduction in pyramidal neuron excitability immediately after binge drinking; however, this hypoexcitability rebounded towards increased pyramidal neuron activity in adulthood in females, suggesting long-term homeostatic adaptations in this circuit. Together, this suggests that binge drinking during key developmental timepoints leads to permanent changes in PL microcircuitry function, which may have broad behavioral implications.

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Section: Methodsmentioning

confidence: 99%

Section: Histology and Sst Cell Countsmentioning

confidence: 99%

Adolescent binge drinking leads to long-lasting changes in cortical microcircuits in mice

Sicher

Starnes

Griffith

et al. 2022

Preprint

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“…Additionally, the stimulation of somatostatin‐expressing GABAergic neurons in the dorsal BNST significantly influenced binge alcohol consumption in female mice but not in males. This stimulation, however, did not result in any changes in anxiety‐like behaviour in either sex 36 . Interestingly, chemogenetic manipulation of corticotropin‐releasing factor and protein kinase C‐δ neurons in the BNST had opposing effects on anxiety‐like behaviours, indicating that functional specificity may be attributed to distinct subdivisions and specific cell types within the BNST 37 …”

Section: Discussionmentioning

confidence: 96%

“…This stimulation, however, did not result in any changes in anxiety-like behaviour in either sex. 36 Interestingly, chemogenetic manipulation of corticotropin-releasing factor and protein kinase C-δ neurons in the BNST had opposing effects on anxiety-like behaviours, indicating that functional specificity may be attributed to distinct subdivisions and specific cell types within the BNST. 37 The PBN has been proposed to play a role in appetite suppression during unfavourable eating conditions.…”

Section: Discussionmentioning

confidence: 99%

Sex‐specific negative affect‐like behaviour and parabrachial nucleus activation induced by BNST stimulation in adult mice with adolescent alcohol history

Albrechet‐Souza,

Kasten,

Bertagna

et al. 2024

Addiction Biology

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Adolescent alcohol use is a strong predictor for the subsequent development of alcohol use disorders later in life. Additionally, adolescence is a critical period for the onset of affective disorders, which can contribute to problematic drinking behaviours and relapse, particularly in females. Previous studies from our laboratory have shown that exposure to adolescent intermittent ethanol (AIE) vapour alters glutamatergic transmission in the bed nucleus of the stria terminalis (BNST) and, when combined with adult stress, elicits sex‐specific changes in glutamatergic plasticity and negative affect‐like behaviours in mice. Building on these findings, the current work investigated whether BNST stimulation could substitute for stress exposure to increase the latency to consume a palatable food in a novel context (hyponeophagia) and promote social avoidance in adult mice with AIE history. Given the dense connections between the BNST and the parabrachial nucleus (PBN), a region involved in mediating threat assessment and feeding behaviours, we hypothesized that increased negative affect‐like behaviours would be associated with PBN activation. Our results revealed that the chemogenetic stimulation of the dorsolateral BNST induced hyponeophagia in females with AIE history, but not in female controls or males of either group. Social interaction remained unaffected in both sexes. Notably, this behavioural phenotype was associated with higher activation of calcitonin gene‐related peptide and dynorphin cells in the PBN. These findings provide new insights into the neurobiological mechanisms underlying the development of negative affect in females and highlight the potential involvement of the BNST‐PBN circuitry in regulating emotional responses to alcohol‐related stimuli.

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“…Furthermore, studies have also shown that SST activity within the BST is associated with binge drinking and fear. Chemogenetic activation of BST SST neurons reduced binge alcohol consumption in female but not in male mice (Suresh Nair et al, 2022). More interestingly, another study uncovered that SST may act as an upstream component of CRH signalling as well, and thus inhibit CRH-mediated stress responses (Stengel & Tache, 2017).…”

Section: Somatostatinmentioning

confidence: 99%

Bed nuclei of the stria terminalis: A key hub in the modulation of anxiety

Wang

Zhang

2023

Eur J of Neuroscience

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The bed nuclei of the stria terminalis (BST) is recognised as a pivotal integrative centre for monitoring emotional valence. It is implicated in the regulation of diverse affective states and motivated behaviours, and decades of research have firmly established its critical role in anxiety‐related behavioural processes. Researchers have recently intricately dissected the BST's dynamic activities, its connection patterns and its functions with respect to specific cell types using multiple techniques such as optogenetics, in vivo calcium imaging and transgenic tools to unmask the complex circuitry mechanisms that underlie anxiety. In this review, we principally focus on studies of anxiety‐involved neuromodulators within the BST and provide a comprehensive architecture of the anxiety network—highlighting the BST as a key hub in orchestrating anxiety‐like behaviour. We posit that these promising efforts will contribute to the identification of an accurate roadmap for future treatment of anxiety disorders.

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Somatostatin neurons in the bed nucleus of the stria terminalis play a sex-dependent role in binge Drinking

Cited by 11 publications

References 47 publications

Adolescent binge drinking leads to long-lasting changes in cortical microcircuits in mice

Adolescent binge drinking leads to long-lasting changes in cortical microcircuits in mice

Sex‐specific negative affect‐like behaviour and parabrachial nucleus activation induced by BNST stimulation in adult mice with adolescent alcohol history

Bed nuclei of the stria terminalis: A key hub in the modulation of anxiety

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