Abstract
In taste buds, the GPCR heterodimer TAS1R2 + TAS1R3 is considered the canonical taste receptor for sugars and noncaloric sweeteners. Nevertheless, evidence has accumulated for the presence of an alternative noncanonical transduction pathway that detects sugars, particularly at high concentration. Sodium-glucose transporter 1 (SGLT1) has been proposed as this transducer, selectively transporting glucose into a subset of taste bud cells which then transmit the signal to taste afferent neurons. To test for TAS1R-independent sweet taste detection, we conducted in vivo Ca(2+) imaging on geniculate ganglion gustatory afferent neurons of Plcb2 knock-out (KO) mice of both sexes. These mice lack an essential signaling effector for TAS1R2 + TAS1R3, thus permitting visualizing signals for an alternative pathway. Indeed, glucose, sucrose, and other sugars evoked responses in Plcb2 KO gustatory afferent neurons but only when presented orally at 1 M. However, glucose, a known substrate for SGLT1, and fructose, not a substrate, elicited equivalent responses. Furthermore, response amplitudes for glucose and fructose were unaffected by varying Na(+) concentration from 0 to 100 mM NaCl, again inconsistent with SGLT1. We also detected sugar-evoked responses in gustatory neurons from normal (heterozygous) mice that were consistent with a "noncanonical" pathway. Such responses were detected in separate neurons from those showing responses mediated by TAS1R2 + TAS1R3. Our results provide neural evidence for noncanonical taste transduction for many sugars but suggest that it may rely on mechanisms other than SGLT1. Most importantly, our data suggest that at least two separate, parallel neural pathways convey information on sweet taste detection from taste buds into the brainstem.