Kang Lai, Class of 2026

Our perception of taste profoundly influences our calorie intake and food preferences, and even serves as a defense mechanism from harmful substances. The gustatory insular cortex, a key brain region associated with taste, is closely linked to eating patterns and disorders. While neuronal circuits in this region have been studied, its neurochemical signaling remains obscure. 

The Maffei lab at Stony Brook University discovered compelling evidence supporting neurosteroid inhibition in regulating taste preference, particularly sweetness. The neurosteroid allopregnanolone (ALLO), which acts as an allosteric modulator, has been linked to elevated appetite or excessive eating, known as hyperphagia. When systemically administered it increases appetite and binge-eating behaviors both in animals and humans. Given this association, researchers hypothesized that ALLO could modulate taste preference and sensitivity by activating receptors within the gustatory cortex.  

ALLO inhibits delta subunit-containing GABAA receptors (d-GABAARs ), heavily expressed in the GABAergic neurons within the gustatory cortex. Using viral injections to genetically knockdown d-GABAARs in mice to inhibit their activity, researchers observed a decreased preference for sucrose, mirroring the effects of ALLO-induced inhibition. In the behavioral paradigm, mice received either an ALLO infusion or saline control and the sucrose-to-water lick ratio was observed. Techniques such as in situ hybridization, electrophysiology, histology, and immunohistochemistry were used to determine the mechanisms behind these behavioral assays. An electrophysiological assessment revealed that the elimination of d-GABAARs in inhibitory neurons abolished both sucrose preference and sensitivity. However, the elimination of d-GABAARs in excitatory pyramidal neurons reduced preference but did not eliminate sensitivity, implying that cell type expressing d-GABAARs plays a role in the magnitude of ALLO’s modulation. 

In subsequent steps, researchers analyzed the codependency of these two neurochemical signaling pathways. While both ALLO injections and d-GABAARs knockdown in flox mice reduced sucrose preference, the Maffei team discovered evidence suggesting the interplay of the two signaling pathways. When ALLO was administered to d-GABAARs knockdown mice there was no change in sucrose preference, supporting that ALLO is dependent on d-GABAARs expression as d-GABAARs is downstream of ALLO in the signaling pathway. 

These findings by the Maffei lab are compelling evidence supporting the importance of neurosteroid inhibitory circuit signaling in taste sensitivity and preferences. The results analyzed in this study on atypical signaling and abnormal levels of ALLO and d-GABAARs reveal their pivotal role as modulators in sweetness preferences and dietary behaviors. Unraveling these biological mechanisms can lead to breakthroughs in treating eating disorders and lead to the exploration of additional neuromodulator-receptor interactions that impact taste sensitivity across other tastes.

Figure 1: Picture of candy

Works Cited: 

[1] Yevoo, P. E., et al. (2025). Modulation of sweet preference by neurosteroid-sensitive, δ-GABAA receptors in adult mouse gustatory insular cortex. Current Biology. Cell Press. https://www.sciencedirect.com/science/article/pii/S096098222500065X?ref=pdf_download&fr=RR-2&rr=91d63db8de844370

[2] Image retrived from https://www.pexels.com/photo/set-of-delicious-jelly-and-caramel-sweets-arranged-in-lines-by-type-4016509/