The question as to whether animals taste cholesterol taste is not resolved. This study investigates whether the fruit fly, Drosophila melanogaster, is capable of detecting cholesterol through their gustatory system. We found that flies are indifferent to low levels of cholesterol and avoid higher levels. The avoidance is mediated by gustatory receptor neurons (GRNs), demonstrating that flies can taste cholesterol. The cholesterol-responsive GRNs comprise a subset that also responds to bitter substances. Cholesterol detection depends on five ionotropic receptor (IR) family members, and disrupting any of these genes impairs the flies' ability to avoid cholesterol. Ectopic expressions of these IRs in GRNs reveals two classes of cholesterol receptors, each with three shared IRs and one unique subunit. Additionally, expressing cholesterol receptors in sugar-responsive GRNs confers attraction to cholesterol. This study reveals that flies can taste cholesterol, and that the detection depends on IRs in GRNs.

Moment-to-moment neural variability has been shown to scale positively with the complexity of stimulus input. However, the mechanisms underlying the ability to align variability to input complexity are unknown. Using a combination of behavioral methods, computational modeling, fMRI, MR spectroscopy, and pharmacological intervention, we investigated the role of aging and GABA in neural variability during visual processing. We replicated previous findings that participants expressed higher variability when viewing more complex visual stimuli. Additionally, we found that such variability modulation was associated with higher baseline visual GABA levels and was reduced in older adults. When pharmacologically increasing GABA activity, we found that participants with lower baseline GABA levels showed a drug-related increase in variability modulation while participants with higher baseline GABA showed no change or even a reduction, consistent with an inverted-U account. Finally, higher baseline GABA and variability modulation were jointly associated with better visual-discrimination performance. These results suggest that GABA plays an important role in how humans utilize neural variability to adapt to the complexity of the visual world.