Lough Kendall J, Knox Jackson C, Moy Sheryl S, King Juliet S, Williams Scott E
Departments of Pathology & Laboratory Medicine and Biology, Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, NC, USA.
Center for Gastrointestinal Biology and Disease, University of North Carolina Chapel Hill, NC, USA.
bioRxiv. 2025 May 7:2025.05.01.651736. doi: 10.1101/2025.05.01.651736.
Gut-brain communication is a key component of homeostasis which regulates behaviors such as appetite and reward. Intestinal enteroendocrine cells (EECs) translate nutrient intake into signals which affect sensation and behavior, in part through synapse-like contacts with vagal nodose neurons. This direct neuroepithelial circuit regulates feeding (1-3), yet its genesis and role in higher order behaviors remains unknown. We find that EECs first contact nodose neurons in utero, and these interactions require brain-derived neurotrophic factor (BDNF). We show that BDNF regulates the dynamics of these interactions, which underlie EEC-evoked optogenetic excitation of the circuit. In addition to feeding, we discover that this circuit regulates sociability and inhibitory behavioral control. These studies define the ontogeny of a direct gut-brain circuit responsible for early physiology and behavior.
肠-脑通讯是体内平衡的关键组成部分，它调节诸如食欲和奖赏等行为。肠道肠内分泌细胞（EECs）将营养物质摄入转化为信号，这些信号部分通过与迷走神经节神经元的突触样接触来影响感觉和行为。这种直接的神经上皮回路调节进食（1-3），但其起源和在更高层次行为中的作用仍不清楚。我们发现EECs在子宫内首次与节神经元接触，并且这些相互作用需要脑源性神经营养因子（BDNF）。我们表明BDNF调节这些相互作用的动态过程，而这些动态过程是EEC诱发的该回路光遗传学兴奋的基础。除了进食，我们还发现这个回路调节社交能力和抑制性行为控制。这些研究确定了一个负责早期生理和行为的直接肠-脑回路的个体发生。
