Figure 2: Silencing the sugar-activated circuit abolishes sugar preference.
a, Fibre photometry monitoring glucose-evoked responses of cNST neurons. The excitatory neurons in the cNST were targeted with GCaMP6s using VGlut2-Cre animals46. b-d, Shown are neural responses following intestinal delivery of glucose, AceK and MDG. Note strong responses to sugar (panel b) and MDG (panel d). The light traces denote normalized 2-trial averages from individual animals, and the dark trace the average of all trials (NR = Normalized Responses). Black bars below traces indicate the time and duration of stimuli. In red are the average responses after bilateral vagotomy (see Methods). Stimuli, 500 mM glucose, 30 mM AceK, 500 mM MDG; n = 4 animals. e, Quantification of neural responses after vagotomy. Two-tailed paired t-test, p = 3 × 10−15 (glucose), p = 5 × 10−13 (MDG), n = 4 animals. Values are mean ± s.e.m. f, Schematic of silencing strategy. TRAP2 animals29 were stimulated with 600 mM glucose to induce expression of Cre-recombinase in the cNST. AAV-DIO-TetTox32 was then targeted bilaterally to the cNST for silencing. g, Silencing the sugar-preference neurons in the cNST does not impair the innate attraction to sugar or sweeteners. The graph shows preference for 600 mM glucose versus water, and preference for 30 mM AceK versus water, n = 6 animals. Values are mean ± s.e.m. h, Sugar-preference graphs (48 h tests) for wildtype mice, demonstrating the robust development of preference for sugar versus sweetener (see also Fig. 1). In contrast, silencing the sugar-activated neurons in the cNST abolishes the development of sugar preference, n = 6 mice, two-sided Mann-Whitney U-Test, p = 4 × 10−4; TetTox-silenced animals consumed as much of the AceK sweetener as they do sugar (see also Extended Data Fig. 5). Values are mean ± s.e.m.