Lateral Hypothalamic GABAergic Neurons Encode and Potentiate Sucrose's Palatability

Abstract

Sucrose is attractive to most species in the animal kingdom, not only because it induces a sweet taste sensation but also for its positive palatability (i.e., oromotor responses elicited by increasing sucrose concentrations). Although palatability is such an important sensory attribute, it is currently unknown which cell types encode and modulate sucrose's palatability. Studies in mice have shown that activation of GABAergic LHAVgat+ neurons evokes voracious eating; however, it is not known whether these neurons would be driving consumption by increasing palatability. Using optrode recordings, we measured sucrose's palatability while VGAT-ChR2 transgenic mice performed a brief access sucrose test. We found that a subpopulation of LHAVgat+ neurons encodes palatability by increasing (or decreasing) their activity as a function of the increment in licking responses evoked by sucrose concentrations. Optogenetic gain of function experiments, where mice were able to choose among available water, 3% and 18% sucrose solutions, uncovered that opto-stimulation of LHAVgat+ neurons consistently promoted higher intake of the most palatable stimulus (18% sucrose). In contrast, if they self-stimulated near the less palatable stimulus, some VGAT-ChR2 mice preferred water over 18% sucrose. Unexpectedly, activation of LHAVgat+ neurons increased quinine intake but only during water deprivation, since in sated animals, they failed to promote quinine intake or tolerate an aversive stimulus. Conversely, these neurons promoted overconsumption of sucrose when it was the nearest stimulus. Also, experiments with solid foods further confirmed that these neurons increased food interaction time with the most palatable food available. We conclude that LHAVgat+ neurons increase the drive to consume, but it is potentiated by the palatability and proximity of the tastant.

Optoception: perception of optogenetic brain stimulation

“…Taken together, these results demonstrate that these mice neglected the 2kHz tone as a cue and used the interoceptive stimuli induced by optogenetic manipulations to guide behavior. We choose LH GABAergic neurons because it is established that they could induce opposing behavioral effects (27,28). For example, in a real-time place preference task, we corroborated that soma stimulation of GABAergic neurons (LH ChR2 ) is rewarding (Figs.…”

“…Taken together, these results proved that these mice neglected the 2kHz tone and used the interoceptive (or any sensory-motor) stimuli induced by optogenetic manipulations to guide behavior. LH GABAergic neurons were chosen because it is well established that they could cause opposing behavioral effects (Garcia et al, 2021;Nieh et al, 2016). For example, in a real-time conditioned place preference task (rtCPP), we corroborated that soma stimulation of GABAergic neurons (LH ChR2 ) is rewarding (Figures 7D-E) in the sense that they preferred the side paired with the laser stimulation, whereas silencing GABAergic neurons (LH ArchT ) was aversive since the mice avoided the side paired with the laser (Figures 7D-E).…”

Photostimulation of Ventral Tegmental Area-Insular Cortex Dopaminergic Inputs Enhances the Salience to Consolidate Aversive Taste Recognition Memory via D1-Like Receptors

“…A BATT measures the oromotor responses (palatability) using the lick rate evoked by tastants during the 5 s reward period ( Villavicencio et al, 2018 ). If dopaminergic neurons are related to taste palatability, we hypothesize that the stimulation would change the lick rate of familiar tastants ( Garcia et al, 2021 ). During this task, mice received either low concentrated saccharin 5 mM, quinine 126 μM, or water for 5 s per trial ( Figure 2A ).…”

“…Mice were water-deprived for 23 h and placed in an operant chamber equipped with a central sipper (Med Associates Inc., Fairfax, VT, United States), where one of three tastants could be delivered (water, quinine 126 μM, or saccharin 5 mM) controlled by a solenoid valve (Parker, Mayfield Heights, OH, United States). In each trial, mice randomly received one tastant for 5 s (2 μl drop in each lick), mice decided whether they lick during the entire reward period ( Garcia et al, 2021 ). To start a new trial, mice needed to refrain from licking for a 1–3 s inter-trial interval (ITI) and lick once again after the ITI was finished.…”

Optoception: Perception of Optogenetic Brain Perturbations

“…Taken together, these results proved that these mice neglected the 2-kHz tone and used any sensation induced by optogenetic manipulations to guide behavior. LH GABAergic neurons were chosen because it is well established that their bidirectional activity caused opposing behavioral effects ( Jennings et al, 2013 ; Nieh et al, 2016 ; Garcia et al, 2021 ). For example, in a rtCPP, we corroborated that bulk soma stimulation of GABAergic neurons (LH ChR2 ) is rewarding ( Fig.…”