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 rather limited. Neuromodulators can affect preferences, though their effects on neural circuits for taste are incompletely understood. Neurosteroids are of particular interest in view of reports that systemic administration of the neurosteroid allopregnanolone, a potent modulator of tonic GABAergic inhibition, induces hyperphagia and increases intake of energy rich food in human and animal subjects. Tonic inhibition is a powerful modulator of circuit excitability and is primarily mediated by extrasynaptic GABA _A receptors containing the delta subunit (δ-GABA _A Rs). These receptors are widely distributed in the brain, but information regarding the expression of δ-GABA _A Rs 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 _A Rs affects sweet taste preference in adult mice. Our data reveal that δ-GABA _A Rs are expressed in multiple cell types within GC. These receptors mediate an allopregnanolone-sensitive tonic current and decrease sweet taste preference by altering the behavioral sensitivity to sucrose concentration in a cell type-specific manner. Our findings demonstrate that taste sensitivity and preference in the adult mammalian brain are modulated by tonic inhibition mediated by neurosteroid-activated δ-GABA _A Rs in GC.