Chemogenetic suppression of NST GABA neurons reveals inhibition of behavioral responses to sucrose and quinine.

Central taste processing begins in the rostral nucleus of the solitary tract (rNST), a region rich in GABAergic neurons. We recently showed that chemogenetic activation of rNST GABA/GAD65 neurons dampens behavioral acceptance of palatable (sucrose and maltodextrin) and increases acceptance of unpalatable (quinine) taste stimuli (Travers et al., 2022). Here, we investigated whether suppressing activity in rNST GABA neurons likewise affects behavioral taste responsivity. Using mice in which Cre was expressed under the control of the GAD65 promoter, we made bilateral rNST injections of a Cre-dependent AAV driving expression of the inhibitory DREADD, hM4Di. Subsequently, we assessed concentration-dependent licking responses to sucrose, quinine, and quinine mixed in 300 mM sucrose. Relative to intraperitoneal injections of saline, clozapine-N-oxide injections significantly increased licking to sucrose and decreased licking to quinine, regardless of whether it was presented alone or mixed in sucrose. Neither oromotor (inter-lick intervals) nor appetitive (number of trials) variables were affected. Consistent with these behavioral effects, the neuronal activity marker, Fos, was expressed in more NST, reticular formation, and parabrachial nucleus cells following clozapine-N-oxide injections. A final experiment compared effects of chemogenetic GABA inhibition on sucrose licking in food deprived versus fed mice. Inhibiting GABA neurons enhanced sucrose licking in both homeostatic states. However, the impact was more marked under the latter state in female mice, suggesting a sex difference in the impact of satiety signals on GABA rNST neurons.