Ali, M. S. S. | bioRxiv Science

bioRxiv2025

Parabrachial Calca neurons influence aversive and appetitive taste function

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.

neuroscience↗

bioRxiv2021

TRPV1-lineage somatosensory fibers communicate with taste neurons in the mouse parabrachial nucleus

Trigeminal neurons supply somatosensation to craniofacial tissues. In mouse brain, ascending projections from medullary trigeminal neurons arrive at taste neurons in the autonomic parabrachial nucleus, suggesting taste neurons participate in somatosensory processing. However, the genetic cell types that support this convergence were undefined. Using Cre-directed optogenetics and in vivo neurophysiology in anesthetized mice of both sexes, here we studied whether TRPV1-lineage nociceptive and thermosensory fibers are primary neurons that drive trigeminal circuits reaching parabrachial taste cells. We monitored spiking activity in individual parabrachial neurons during photoexcitation of the terminals of TRPV1-lineage fibers that arrived at the dorsal spinal trigeminal nucleus pars caudalis, which relays orofacial somatosensory messages to the parabrachial area. Parabrachial neural responses to oral delivery of taste, chemesthetic, and thermal stimuli were also recorded. We found that optical excitation of TRPV1-lineage fibers frequently stimulated traditionally defined taste neurons in lateral parabrachial nuclei. The tuning of neurons across diverse tastes associated with their sensitivity to excitation of TRPV1-lineage fibers, which only sparingly engaged neurons oriented to preferred tastes like sucrose. Moreover, neurons that responded to photostimulation of TRPV1-lineage afferents showed strong responses to temperature including noxious heat, which predominantly excited parabrachial bitter taste cells. Multivariate analyses revealed the parabrachial confluence of TRPV1-lineage signals with taste captured sensory valence information shared across aversive gustatory, nociceptive, and thermal stimuli. Our results reveal that trigeminal fibers with defined roles in thermosensation and pain communicate with parabrachial taste neurons. This multisensory convergence supports dependencies between gustatory and somatosensory hedonic representations in the brain.

neuroscience↗