(July 12th) A new insight on gut-brain axis using wireless optogenetics

Over the past several decades, obesity has grown into a major global epidemic. In the United States, more than two-thirds of adults are now overweight and one-third is obese. Unfortunately, the current available treatments for obesity are often ineffective, and do not treat the underlying pathology. Moreover, therapies for these conditions are limited by our inability to understand and control the network of neuronal circuitry, in particular vagus afferent fibers, that regulate energy homeostasis. Meal cessation is to a large extent mediated by feedback from the gut to the brain. Distension of the stomach, the absorption of nutrients and the release of satiety hormones (GLP-1, peptide YY, and cholecystokinin) cells can activate the vagus nerve that then signals the nucleus tractus solitarius (NTS) in the hindbrain. Neurons in NTS then relay signals to the parabrachial nucleus (PBN) and other nuclei to suppress feeding. Because the vagus is a major origin of satiation signals, it is a logical place to intervene to treat obesity. Furthermore, several studies indicate that the vagus becomes insensitive to satiation signals in obese animals. Consequently, the ability to bypass this obesity-induced insensitivity and experimentally activate the vagus has significant potential. However, a human nodose ganglion contains 100,000 neurons which can innervate many different internal organs. Therefore, cellular level control of nerves is crucial to this pursuit. In addition, there is no way to directly record the activity of vagal neurons in awake mice, which can provide real insights into how satiety information is processed. Thus, all the experiments that suggest that the vagus becomes insensitive to nutrients and hormones in response to obesity are indirect. Here, we propose soft, miniaturized implantable battery-free wireless device that can offer exceptional spatial/temporal resolution, optogenetic stimulation, and capabilities in wireless recording. These innovative and disruptive technologies allow experiments that examine subtypes suppressing feeding, thereby identifying a signaling pathway that could regulate food intake to treat obesity. Here, we use adult male mice (C57/BI6 background) for experiments and inject AAV9-Syn-DIO-ChrimsonR-TdTomato virus into nodose ganglion to infect vagus nerve.