Highly Selective Brain-To-Gut Communication via Genetically Defined Vagus Neurons

Abstract

The dorsal motor nucleus of the vagus (DMV) is the primary source of parasympathetic input to the digestive system and innervates many digestive organs. However, its organizational principles are poorly understood and it’s unclear whether vagal motor neurons project broadly to all digestive organs or if there are subtypes of vagal motor neurons that project to specific regions of the digestive system as “labeled lines” to perform specific functions. To better understand how the motor vagus nerve controls digestion, we performed single-nucleus RNA- sequencing on cholinergic DMV neurons and identified seven molecularly-distinct subtypes of vagal motor neurons. Next, we assembled or generated recombinase-driver mice that provide genetic access to each DMV neuron subtype. In an initial manuscript, we showed that two of these DMV neuron subtypes exclusively innervate a specific region of the digestive system and target neurochemically-distinct subtypes of enteric neurons. We next focused on characterizing three additional DMV neuron subtypes. Collectively, our data supports the model that the DMV consists of multiple genetically defined labeled lines that project to discrete regions of the digestive system and target neurochemically-distinct subtypes of enteric neurons.