Non-canonical Taste Transduction of Sugars Elicits Responses in a Dedicated Subset of Gustatory Afferent Neurons

In taste buds, the GPCR heterodimer TAS1R2+TAS1R3, is considered the canonical taste receptor for sugars and non-caloric sweeteners. Nevertheless, evidence has accumulated for the presence of an alternative non-canonical 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 this role of SGLT1, we conducted in vivo Ca 2+ imaging on geniculate ganglion gustatory afferent neurons of Plcb2 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 1M. However, glucose, a known substrate for SGLT1, and fructose, not a substrate, elicited equivalent responses. Further, 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 “non-canonical” pathway. Such responses were detected in separate neurons from those showing responses mediated by TAS1R2+TAS1R3. Our results provide neural evidence for non-canonical 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. Significance Statement The G protein-coupled receptor heterodimer, TAS1R2+TAS1R3, is activated by many sugars and is considered the cardinal sweet taste receptor in taste buds. Yet, mice can detect certain sugars in the absence of this receptor. We performed in vivo Ca 2+ imaging of peripheral gustatory neurons in mice that lack a protein, PLCβ2, essential for transduction by TAS1Rs (i.e. Plcb2 knockout mice). Here, we show TAS1R-independent neuronal responses to sugars. We show that these responses lack certain features of a previously proposed alternative transducer, sodium-glucose transporter 1 (SGLT1). Importantly, we present evidence that neurons exhibiting TAS1R-independent responses to sugars may form a separate neural pathway, parallel to TAS1R-mediated transduction, for conveying information from taste buds to brainstem.