Genetic Identification of Vagal Sensory Neurons That Control Feeding

Organ-specific, multimodal, wireless optoelectronics for high-throughput phenotyping of peripheral neural pathways

“…Surprisingly, we did not observe differences in place preference or avoidance (Fig. 4e,f), similar to optogenetic stimulation of other vagal afferent cell-types that innervate the gastrointestinal tract 14 . Conversely, an open-eld assay demonstrated that optogenetic stimulation reduced the time mice spend in the center, indicative of anxiety-like behavior and suggesting that activation of Calca+ gastric vagal afferent bers might be aversive (Fig.…”

“…Prior methods for optogenetic activation of vagal afferents in awake mice have either lacked organ speci city 14 or involved gut injections of a retrogradely transported opsin virus and ber-optic implantation in the hindbrain where vagal afferents terminate 4 . While the latter provides organ speci city, retrograde viruses can be limited by tropism and incomplete infection of certain cell types.…”

“…A recent study identi ed genetically distinct vagal afferent neurons in the nodose ganglion that innervate the stomach and express either Calca, Sst, Gpr65, or Glp1r genes 14 . In contrast to Sst and Gpr65, which exhibit either mechanosensitive morphological endings in muscle layers (Glp1r) or chemosensitive endings in the mucosal layer (Sst, Gpr65), Calca+ neurons form spatially-restricted chemosensitive mucosal endings in the corpus versus mechanosensitive intramuscular arrays in the stomach antrum 14 .…”

Nutrient sensing in the nucleus of the solitary tract mediates non-aversive suppression of feeding via inhibition of AgRP neurons

“…Recent work indicates that AgRP neurons integrate various sensory inputs including environmental food-related cues and visceral mechanosensory and nutritional inputs (Bai et al, 2019; Betley et al, 2015; Beutler et al, 2017; Mandelblat-Cerf et al, 2015). Our work extends the integrative capability of AgRP neurons to include brainstem nutrient sensing inputs.…”

“…Addressing this question with molecularly-defined circuit analysis tools is difficult because most identified NTS neurochemical subsets are functionally heterogeneous, respond to multiple cues and project widely throughout the neuraxis (D’Agostino et al, 2016; Rinaman, 2010). Instead, it may be possible to better understand the functional organization of NTS feeding-regulatory circuits using functionally-defined circuit mapping, which could be particularly insightful if subsets of NTS neurons are specialized in the transmission of highly specific sensory cues and organized in a similar fashion as gustatory and vagal sensory neurons (Bai et al, 2019; Williams et al, 2016). Applying such a strategy to signals able to produce satiation or satiety without negative consequences may lead to important new understanding of how to pharmacologically suppress appetite without undesirable side effects.…”