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 Calca gene support sensory-integrative responses, albeit only limited data have addressed their influence on taste. Here we studied how chemogenetic dampening of PB-Calca neurons impacted 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 CalcaCre/+ mice induced expression of the inhibitory designer receptor hM4Di:mCherry (hM4Di mice) or fluorophore mCherry alone (mCherry mice) in PB-Calca neurons. Several weeks later, hM4Di and mCherry mice entered brief-access tests where they could lick taste solutions on discrete seconds-long trials. Stimuli included the behaviorally avoided, but functionally different, bitter taste stimuli quinine (0 [water], 0.1, 0.3, and 1.0 mM) and cycloheximide (0, 0.001, 0.003, and 0.01 mM), and the appetitive sugar sucrose (0, 100, 300, 500, and 1000 mM). Both hM4Di and mCherry mice received the hM4Di ligand clozapine-N-oxide (CNO, 5 mg/kg, i.p.) prior to daily tests performed by blinded experimenters. With CNO, hM4Di mice displayed greater average licking (i.e., less avoidance) of quinine (p < 0.05), but not cycloheximide (p > 0.3), than mCherry mice, implying PB-Calca neurons variably influence orosensory responses across bitter stimuli. Moreover, male hM4Di mice selectively showed reduced mean licking preferences for sucrose under CNO (p < 0.05). These data suggest that PB-Calca neurons participate in both aversive and appetitive taste-guided behaviors, with their role in appetitive taste dependent on sex.