Parabrachial Calca Neurons Influence Aversive and Appetitive Taste Function

Abstract

The parabrachial (PB) nucleus participates in taste processing and integration with other senses. PB neurons that express the <i>Calca</i> gene support sensory-integrative responses, albeit only limited data have addressed their influence on taste. Here we investigated how chemogenetic dampening of PB-<i>Calca</i> neurons affected mouse orosensory preferences for diverse taste stimuli in brief-access fluid exposure tests, which capture oral sensory/tongue control of licking behavior. Intracranial delivery of Cre-dependent viruses in female and male <i>Calca</i> ^Cre/+ mice induced expression of the inhibitory designer receptor hM4Di:mCherry (hM4Di mice) or fluorophore mCherry alone (mCherry control mice) in PB-<i>Calca</i> neurons. Several weeks later, hM4Di and mCherry mice entered brief-access tests where they could lick solutions during discrete, seconds-long trials. Stimuli included concentration series of the behaviorally avoided bitter taste stimuli quinine and cycloheximide, the appetitive sugar sucrose, and mildly cool water and less preferred innocuous warm water. Blinded experimenters administered the hM4Di ligand clozapine-<i>N</i>-oxide (CNO) to all hM4Di and mCherry mice prior to daily tests. With CNO, hM4Di mice displayed greater average licking (i.e., less avoidance) of quinine than mCherry mice (<i>p</i> < 0.05). Moreover, male hM4Di mice selectively showed reduced mean licking preferences for sucrose under CNO (<i>p</i> < 0.05). These data suggest that PB-<i>Calca</i> neurons participate in both aversive and appetitive taste-guided behaviors, with their role in appetitive taste dependent on sex. Finally, orosensory responses to cycloheximide and thermal-controlled water did not differ (<i>p</i> > 0.05) between hM4Di and mCherry mice under CNO. Results are discussed considering functional differences among stimuli and study limitations.