Fri, Nov 20 (10.15 AM – 10.35 AM)
Coupling of Prefrontal Cortical Activity to Arousal Predicts Alcohol Consumption
Alcohol use disorder (AUD) exacts a major societal toll. AUD is highly comorbid with neuropsychiatric conditions characterized by hyperarousal (e.g., posttraumatic stress disorder), suggesting common underlying mechanisms. Top-down control from the prefrontal cortex (PFC), a critical hub for executive, cognitive, and emotional functions, is key for the regulation of alcohol consumption. Arousal exerts profound effects on cortical processing by engaging neuromodulation of excitatory and specific inhibitory cell types. Despite this, it is unclear whether and how arousal-mediated modulation of PFC circuits relates to alcohol drinking behaviors. Two-photon microscopy is ideally suited for studying cell-specific circuits. We addressed a major limitation of this technology by developing a novel behavioral paradigm for drinking in head-fixed mice. We recorded responses of layer 2/3 excitatory neurons in the PFC as mice voluntarily consumed alcohol, along with video recording of the pupil to track momentary fluctuations in arousal. Remarkably, we found that the coupling of arousal to ACC activity predicted the amount of alcohol consumed. This unique combination of technical and conceptual advances identifies cortical coupling to arousal as a potential biomarker for alcohol drinking and lay the groundwork for future studies to dissect the contribution of specific circuits in this process.
Fri, Nov 20 (11.05 AM – 11.25 AM)
Hypothalamic Glucose Sensing Neurons: Multiple functions, One goal
Since the brain is an obligate consumer of glucose, it is teleologically advantageous to have evolved neurons capable of sensing and responding to changes in extracellular glucose. Glucose-excited (GE) and glucose-inhibited (GI) neurons exist throughout the brain. Today’s talk will focus on GI neurons in the ventromedial (VMH) and lateral (LH) hypothalamus. We have strong evidence that VMH GI neurons serve as part of an alarm system that raises blood glucose levels during life-threatening hypoglycemia. However, we hypothesize that these neurons serve multiple physiological roles in maintaining an adequate glucose supply for the brain. The evidence for a role of VMH GI neurons in maintaining fasting glucose levels as well as inhibiting processes that increase energy expenditure will be discussed. We further hypothesize that the LH orexin-GI neurons play a role in behaviors such as reward-based feeding and contribute to the difficulty maintaining weight loss after dieting. LH orexin-GI neurons may also play a role in wakefulness and arousal. Together, these data suggest a much more complex role for hypothalamic GI neurons in glucose homeostasis than simply as protection against iatrogenic insulin-induced hypoglycemia.