Biology subjects

Rogers, E. T.

Publications and source records attributed to Rogers, E. T..

3 recordsLinked to original sources

bioRxiv2025

A Distinct Subpopulation of Extended Amygdala Neurons Drives Food Intake

BackgroundNeurons in the oval subnucleus of the bed nucleus of the stria terminalis (ovBNST) integrate stress and reward signals to regulate motivated behaviors, including food consumption. However, the contribution of specific ovBNST neuronal subpopulations remains poorly understood. Here, we investigated vasoactive intestinal peptide receptor 2 (Vipr2) expressing ovBNST neurons using chemogenetics, immunohistochemistry, and viral circuit mapping. Methods and ResultsUsing stimulatory hM3Dq designer receptors exclusively activated by designer drugs (DREADDs), we found that chemogenetic activation of ovBNSTVipr2neurons significantly increased food intake. We then quantified cFos activation in Vipr2-tdTomato reporter mice following several unique feeding-related manipulations, finding that food restriction (FR) robustly activated ovBNSTVipr2 neurons. Further analysis revealed decreased vasoactive intestinal peptide (VIP) innervation of the ovBNST following FR, in which reduced VIP expression was significantly associated with greater ovBNSTVipr2 cFos activation. Given previous reports of reduced food intake following stimulation of ovBNST neurons expressing protein kinase C delta (PKC{delta}), we used immunostaining to uncover that Vipr2 and PKC{delta} mark largely non-overlapping ovBNST neuronal subpopulations, aligning with their opposing effects on food intake. Finally, Cre-dependent anterograde viral tracing revealed that ovBNSTVipr2 neurons project prominently to the parasubthalamic nucleus (PSTN) and paraventricular nucleus of the hypothalamus (PVN), two feeding-related regions. ConclusionsTogether, these results identify ovBNSTVipr2neurons as a functionally distinct BNST subpopulation that promotes feeding, is activated by food restriction, and links ovBNST neuropeptide signaling to hypothalamic feeding centers.

neuroscience↗

bioRxiv2025

Early life stress modulates behavioral sensitivity to alcohol and promotes escalation of alcohol drinking

Adverse childhood experiences significantly increase the risk of developing alcohol use disorder (AUD) in adulthood. We used a model of combined limited bedding/nesting and maternal separation (LBN+MS) in C57BL/6J background mice to investigate how early life stress (ELS) modulates behavioral sensitivity to alcohol, long-term alcohol drinking patterns, and the effects of alcohol on social behaviors. Our findings reveal that ELS increased sensitivity to the stimulatory locomotor effects of alcohol (1.75 g/kg) selectively in females and reduced sensitivity to the sedative effects of alcohol (4.0 g/kg) particularly in males. This pattern of enhanced stimulation and diminished sedation is consistent with phenotypes observed in human subjects at high risk for developing AUD. ELS also significantly enhanced escalation of voluntary alcohol intake and preference over eight weeks of two-bottle choice intermittent access drinking particularly in males. Additionally, social behavior assessments revealed that ELS impaired sociability selectively in females with a history of alcohol drinking, highlighting the detrimental interactive effects of ELS and alcohol exposure on adaptive behaviors. These results underscore the complex interplay between ELS, alcohol responses, and sex differences, suggesting that ELS creates a high-risk phenotype for AUD through altered alcohol behavioral sensitivity. Our study highlights the importance of future studies that seek to identify the neurobiological mechanisms underlying these interactions, which may pave the way for targeted interventions in populations affected by childhood adversity and excessive alcohol consumption.

neuroscience↗

bioRxiv2024

Sex-Specific Roles of Hypocretin Receptor Signaling in CRF Neurons on Alcohol Drinking, Anxiety, and BNST Neuronal Excitability

Alcohol use disorder (AUD) is characterized by compulsive alcohol consumption and negative emotional states during withdrawal, often perpetuating a cycle of addiction through arousal dysfunction. The hypocretin/orexin (Hcrt) neuropeptide system, a key regulator of arousal, has been implicated in these processes, particularly in its interactions with corticotropin-releasing factor (CRF) neurons within the bed nucleus of the stria terminalis (BNST). We investigated the role of Hcrt receptor signaling in CRF neurons in modulating alcohol intake, anxiety behaviors, and BNST excitability, with a focus on sex-specific differences. Using CRF-specific genetic deletion of HcrtR1 and/or HcrtR2 receptors in mice, we found that deletion of HcrtR1 significantly reduced alcohol intake, with sex-specific effects on BNST excitability. CRF-specific HcrtR2 deletion, while not affecting alcohol consumption, decreased baseline anxiety-like behaviors in males relative to females. Moreover, the double deletion of both Hcrt receptors from CRF neurons led to reduced alcohol drinking in males and dampened anxiety behaviors and BNST excitability in both sexes during protracted withdrawal. These findings suggest that Hcrt signaling in CRF neurons plays a critical role in the persistence of excessive alcohol consumption and the development of negative affective states, with distinct contributions from HcrtR1 and HcrtR2. The observed sex-specific differences underscore the need for tailored therapeutic approaches targeting the Hcrt system in the treatment of AUD.

neuroscience↗