Modulation of sweet preference by neurosteroid-sensitive, δ-GABA_A receptors in adult mouse gustatory insular cortex

Taste preference is a fundamental driver of feeding behavior, influencing dietary choices and eating patterns. Extensive experimental evidence indicates that the gustatory cortex (GC) is engaged in taste perception, palatability, and preference. However, our knowledge of the neural and neurochemical signals regulating taste preference is limited. Neuromodulators can affect preferences, though their effects on neural circuits for taste are incompletely understood. Neurosteroids are of particular interest, as systemic administration of the neurosteroid allopregnanolone (ALLO), a positive allosteric modulator of extrasynaptic GABA_A receptors containing the delta subunit (δ-GABA_ARs), induces hyperphagia and increases intake of energy-rich food in humans and animals. The δ-GABA_ARs receptors produce a tonic inhibitory current and are widely distributed in the brain. However, information regarding their expression within gustatory circuits is lacking, and their role in taste preference has not been investigated. Here, we focused on GC to investigate whether activation of δ-GABA_ARs affects sweet taste preference in adult mice. Our data reveal that δ-GABA_ARs are expressed in multiple cell types within GC, mediate an ALLO-sensitive tonic current, decrease the behavioral sensitivity to sucrose, and reduce the preference for sweet taste in a cell-type-specific manner. Our findings demonstrate a fundamental role for δ-GABA_AR-mediated currents within GC in regulating taste sensitivity and preference in the adult mammalian brain.