Characteristics and Impact of the rNST GABA Network on Neural and Behavioral Taste Responses

ABSTRACT The rostral nucleus of the solitary tract (rNST), the initial CNS site for processing gustatory information, is comprised of two major cell types, glutamatergic excitatory and GABAergic inhibitory neurons. Many investigators have described taste responses of rNST neurons, but the phenotypes of these cells were unknown. The current investigation used mice expressing ChR2 under the control of GAD65, a synthetic enzyme for GABA. In vivo single-unit recording of rNST cells during optogenetic stimulation allowed us to address two important questions: (1) what are the gustatory response characteristics of “optotagged”, putative GABAergic (G+ TASTE ) neurons? and (2) how does optogenetic activation of the rNST GABA network impact taste responses in non-GABAergic (G- TASTE ) neurons? We observed that chemosensitive profiles of G+ TASTE neurons were similar to non-GABA taste neurons but had much lower response rates. We further observed that there was a population of GABA cells unresponsive to taste stimulation (G+ UNR ) and located more ventrally in the nucleus. Activating rNST inhibitory circuitry suppressed gustatory responses of G- TASTE neurons across all qualities and types of chemosensitive neurons. Tuning curves were modestly sharpened but the overall shape of response profiles and the ensemble pattern remained highly stable. These neurophysiological effects were consistent with the behavioral consequences of activating GAD65-expressing inhibitory neurons using DREADDs. In a brief-access licking task, concentration-response curves to both palatable (sucrose, maltrin) and unpalatable (quinine) stimuli were shifted to the right when GABA neurons were activated. Thus, the rNST GABAergic network is poised to modulate taste intensity across the qualitative and hedonic spectrum. SIGNIFICANCE STATEMENT The rNST, the CNS gateway for taste, is rich in GABAergic neurons and synapses. Our in vivo recordings from GAD65/ChR2 mice reveal that gustatory response profiles of optotagged GABAergic neurons resemble non-GABAergic neurons, but with much reduced amplitudes. A novel population of GABA neurons were unresponsive to oral stimulation suggesting they are targets for centrifugal influences. Activating rNST inhibitory circuitry modestly sharpened gustatory tuning but preserved the ensemble pattern for taste quality despite markedly suppressed responses. In behaving mice, activating rNST GAD65-expressing neurons with DREADDs shifted response-concentration curves for palatable and unpalatable stimuli, but preserved appropriate behaviors. These observations unveil previously unknown features of rNST GABA cells and demonstrate substantial inhibitory modulation at the first central taste relay.