A Neural Circuit for Gut-Induced Reward

The gut is now recognized as a major regulator of motivational and emotional states. However, the relevant gut-brain neuronal circuitry remains unknown. We show that optical activation of gut-innervating vagal sensory neurons recapitulates the hallmark effects of stimulating brain reward neurons. Specifically, right, but not left, vagal sensory ganglion activation sustained self-stimulation behavior, conditioned both flavor and place preferences, and induced dopamine release from Substantia nigra. Cell-specific transneuronal tracing revealed asymmetric ascending pathways of vagal origin throughout the CNS. In particular, transneuronal labeling identified the glutamatergic neurons of the dorsolateral parabrachial region as the obligatory relay linking the right vagal sensory ganglion to dopamine cells in Substantia nigra. Consistently, optical activation of parabrachio-nigral projections replicated the rewarding effects of right vagus excitation. Our findings establish the vagal gut-to-brain axis as an integral component of the neuronal reward pathway. They also suggest novel vagal stimulation approaches to affective disorders.

如今，肠道已被认定为动机与情绪状态的关键调节枢纽。然而，与之相关的肠-脑神经元环路至今仍未明确。本研究证实，对支配肠道的迷走感觉神经元（vagal sensory neurons）进行光激活（optical activation），可复现刺激脑内奖赏神经元所产生的典型效应。具体而言，激活右侧而非左侧的迷走感觉神经节（vagal sensory ganglion），能够维持自我刺激行为，诱导条件性味觉偏好与条件性位置偏好，并引发黑质（Substantia nigra）的多巴胺释放。采用细胞特异性跨神经元追踪（transneuronal tracing）技术，研究人员发现迷走神经起源的不对称上行通路遍布整个中枢神经系统（central nervous system, CNS）。尤为关键的是，跨神经元标记（transneuronal labeling）技术证实，背外侧臂旁区（dorsolateral parabrachial region）的谷氨酸能神经元（glutamatergic neurons）是连接右侧迷走感觉神经节与黑质多巴胺能神经元的必需中继节点。与之相一致的是，激活臂旁黑质投射（parabrachio-nigral projections）可复现右侧迷走神经兴奋所带来的奖赏效应。本研究结果确立了迷走神经肠-脑轴作为神经元奖赏通路的核心组成部分的地位。同时，本研究也为情感障碍（affective disorders）的新型迷走神经干预策略提供了全新方向。