Kaya Ekin, Wegienka Evan, Akhtarzandi-Das Alexandra, Do Hanh, Eban-Rothschild Ada, Rothschild Gideon
Department of Psychology, University of Michigan, Ann Arbor, United States.
Kresge Hearing Research Institute and Department of Otolaryngology, Head and Neck Surgery, University of Michigan, Ann Arbor, United States.
Elife. 2025 Apr 14;14:RP105059. doi: 10.7554/eLife.105059.
Effective regulation of energy metabolism is critical for survival. Metabolic control involves various nuclei within the hypothalamus, which receive information about the body's energy state and coordinate appropriate responses to maintain homeostasis, such as thermogenesis, pancreatic insulin secretion, and food-seeking behaviors. It has recently been found that the hippocampus, a brain region traditionally associated with memory and spatial navigation, is also involved in metabolic regulation. Specifically, hippocampal sharp wave-ripples (SWRs), which are high-frequency neural oscillations supporting memory consolidation and foraging decisions, have been shown to reduce peripheral glucose levels. However, whether SWRs are enhanced by recent feeding-when the need for glucose metabolism increases, and if so, whether feeding-dependent modulation of SWRs is communicated to other brain regions involved in metabolic regulation-remains unknown. To address these gaps, we recorded SWRs from the dorsal CA1 region of the hippocampus of mice during sleep sessions before and after consumption of meals of varying caloric values. We found that SWRs occurring during sleep are significantly enhanced following food intake, with the magnitude of enhancement being dependent on the caloric content of the meal. This pattern occurred under both food-deprived and ad libitum feeding conditions. Moreover, we demonstrate that GABAergic neurons in the lateral hypothalamus, which are known to regulate food intake, exhibit a robust SWR-triggered increase in activity. These findings identify the satiety state as a factor modulating SWRs and suggest that hippocampal-lateral hypothalamic communication is a potential mechanism by which SWRs could modulate peripheral metabolism and food intake.
有效的能量代谢调节对生存至关重要。代谢控制涉及下丘脑内的多个核团，这些核团接收有关身体能量状态的信息，并协调适当的反应以维持体内平衡，如产热、胰腺胰岛素分泌和觅食行为。最近发现，海马体，一个传统上与记忆和空间导航相关的脑区，也参与代谢调节。具体而言，海马体的尖波涟漪（SWRs），即支持记忆巩固和觅食决策的高频神经振荡，已被证明可降低外周葡萄糖水平。然而，SWRs是否在近期进食后增强——此时葡萄糖代谢需求增加，如果是这样，进食依赖性的SWRs调节是否会传递到参与代谢调节的其他脑区——仍然未知。为了填补这些空白，我们在小鼠食用不同热量值的餐后睡眠期间，记录了海马体背侧CA1区的SWRs。我们发现，进食后睡眠期间出现的SWRs显著增强，增强幅度取决于餐食的热量含量。这种模式在食物剥夺和自由进食条件下均会出现。此外，我们证明，已知调节食物摄入的下丘脑外侧的GABA能神经元，在SWRs触发下活动会显著增加。这些发现确定饱腹感状态是调节SWRs的一个因素，并表明海马体-下丘脑外侧的通信是SWRs调节外周代谢和食物摄入的一种潜在机制。
