Extended Data Fig. 2: Vagal neuron response to sugars depends on intestinal Cck-labeled neuropod cells, related to Figs. 2 and 3.

a, In wild-type vagal nodose neurons loaded with Fluo-4 and Fura Red, calcium activity was imaged in response to d-glucose [20 mM], sucralose [2 mM], maltodextrin [1%], and positive control KCl [50 mM] (N = 3 mice; n = 59 neurons). b, In CckCRE_tdTomato vagal nodose neurons cultured alone, current was recorded to a+40mV pulse, d-glucose [20 mM] stimulus, or sucralose [2 mM] stimulus (N = 2 mice; n = 15 neurons). No current response was observed to d-glucose or sucralose. Data are presented as mean values. Error bars = S.E.M. c, Left- Electrophysiology in co-cultures of vagal nodose neurons and CckCRE_tdTomato intestinal cells (bar = 10 μm). Center- Of 18 pairs of co-cultured neurons, excitatory post-synaptic potentials were recorded to d-glucose [20 mM] (44.4%), sucralose [2 mM] (22.2%), and both (33.3%) (N = 3 mice, n = 18 pairs). Right - Peak excitatory post-synaptic currents to d-glucose [20 mM] and sucralose [2 mM] (N = 3 mice; n = 18 pairs). Data are presented as mean values. Error bars = S.E.M. d, Single cell transcriptomic data projected onto the vagal nodose atlas⁶¹ showing 18 nodose ganglia (NG) and 6 jugular ganglia (JG) clusters (N = 5R, 6L nodose ganglia; n = 5,507 cells). e, Violin plots from single cell transcriptomic data showing transcripts for Slc5a1 (SGLT1), Tas1r2, Tas1r3, and control Slc17a6 (VGLUT2)—a peripheral afferent marker found ubiquitously in nodose and jugular ganglion neurons.