Anatomical and functional communication between vagal sensory neurons and pancreatic islet β-cells in mice

FARE Award Winner

Authors

• S Kumar
• SG Rane

Abstract

Brain and the gastrointestinal tract communicate via complex bidirectional processes. This higher order communication includes, but is not limited to, the parasympathetic (via the vagus nerve) and the sympathetic (via the prevertebral ganglia) arms of the autonomic nervous system. The role of the autonomic nervous system in metabolism and associated disorders is poorly understood due to insufficient understanding of the neural pathways that communicate with internal organs. Vagal sensory neurons (VSNs) are known to innervate the brain and the peripheral organs. However, the anatomical and functional details of these communications are unclear and, hence, are the focus of my research. My preliminary experiments using monosynaptic tracing in combination with RNAscope methods suggest the existence of molecularly diverse types of VSNs innervating pancreatic islet β-cells in mice. More specifically, I find that the VSNs anatomically connected to insulin producing β-cells express cocaine- and amphetamine-regulated transcript (CART). Further, I observed that CART-positive axons densely innervate the pancreatic islets. The preliminary results on the functional aspects of this vagal CART neuron − islet β-cell circuit suggest a role in glucose homeostasis and food intake that depend on the metabolic state of the mice. Specifically, via chemogenetics approaches in combination with automated glucose telemetry, I find that activation of vagal CART neurons modifies blood glucose levels. Further, optogenetics stimulation of vagal CART neuron terminals in the brainstem alter food consumption. Delineating the vagal sensory complex-endocrine pancreas communications will unravel a central–peripheral neuronal circuitry vital to glucose homeostasis and metabolic disorders.

Scientific Focus Area: Neuroscience

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