Genetic Deletion of TrpV1 and TrpA1 Does not Alter Avoidance of or Patterns of Brainstem Activation to Citric Acid in Mice

Abstract

1Exposure of the oral cavity to acidic solutions evokes not only a sensation of sour, but also of 2 sharp or tangy. Acidic substances potentially stimulate both taste buds and acid-sensitive 3 mucosal free nerve endings. Mice lacking taste function (P2X2/P2X3 double-KO mice) refuse 4 acidic solutions similarly to wildtype mice and intraoral infusion of acidic solutions in these KO 5 animals evokes substantial c-Fos activity within orosensory trigeminal nuclei as well as of the 6 nucleus of the solitary tract (nTS) (Stratford et. al 2017). This residual acid-evoked, non-taste 7 activity includes areas that receive inputs from trigeminal and glossopharyngeal peptidergic 8 (CGRP-containing) nerve fibers that express TrpA1 and TrpV1 both of which are activated by 9 low pH. We compared avoidance responses in wildtype (WT) and TrpA1/V1 double KO 10 (TRPA1/V1 Dbl-/-) mice in brief-access behavioral assay (lickometer) to 1, 3, 10, 30 mM citric 11 acid, along with 100 µM SC45647 and H2O. Both WT and TRPA1/V1 Dbl-/show similar 12 avoidance, including to higher concentrations of citric acid (10 and 30 mM; pH 2.62 and pH 2.36 13 respectively), indicating that neither TrpA1 nor TrpV1 is necessary for the acid avoidance 14 behavior in animals with an intact taste system. Similarly, induction of c-Fos in the nTS and 15 dorsomedial spinal trigeminal nucleus was similar in the WT and TRPA1/V1 Dbl-/animals. 16 Taken together these results suggest non-TrpV1 and non-TrpA1 receptors underlie the residual 17 responses to acids in mice lacking taste function. 18 19