Project Summary As animals transition from relying on their mother’s milk to foraging and consuming foods, they experience a large variety of new tastants. These experiences regulate their taste preferences later in life through a process that likely relies on plasticity in neural circuits associated with taste and feeding. The gustatory cortex (GC) is involved in processing taste information. It is required for taste-motivated behaviors and for learning about the chemosensory and affective dimensions of gustatory stimuli. The effects of early experiences with tastants on the development of taste preferences or the maturation of GC circuits has not been investigated. Our previous work in a different sensory cortex demonstrated a central role for inhibitory neurons in experience-dependent plasticity and postnatal circuit refinement. In this proposal, we will take advantage of our previous work and set out to investigate how the maturation of inhibition in GC contributes to the expression of taste preferences. The first part of the proposal will determine how taste preferences mature over the course of postnatal development and assess the role of experience with tastants on the modulation of taste preferences. Our preliminary observations suggest that there is a sensitive period for the experience-dependent modulation of taste preferences that is restricted to the weeks between the time weaning and young adulthood. We will also assess the time course of maturation of inhibitory circuits in GC and their sensitivity to experience with tastants. Finally, we will assess the relationship between the maturation of inhibition and the development of taste preferences using a variety of approaches including enzymatic and chemogenetic manipulations of inhibitory circuits’ maturation. These studies will determine the role of inhibitory circuit in GC in the behavioral expression of taste preferences. While mechanisms underlying learning about the value or physical cues associated with tastes has been investigated in adulthood, the mechanisms leading to such a refined circuit in postnatal development have not been described. The results of these studies will indicate the role of early food experiences in determining taste-based choices throughout life.