Project summary The sense of taste is associated with food appeal and feeding preferences in diverse animals. Taste preferences have ties to human ingestive disorders that impact nutritional status and health. Yet the neural basis by which taste sensations drive ingestive preference or avoidance remains only poorly understood. A central question concerns how the brain represents information about taste hedonics. In rodents, neural messages for taste arrive at the brain stem parabrachial nuclei. Parabrachial neurons are partly multimodal. Recent data from our lab show gustatory sensations stimulate neurons in parabrachial regions that integrate aversive sensory and nociceptive messages from afferents across the body. Our goal here is to understand if taste messages are processed by broadly integrative neurons in the parabrachial complex that communicate with the amygdala, and if traditionally defined taste neurons constitute a subpopulation of these cells. These questions have key implications for understanding the functional organization of gustatory circuits and the neural basis of hedonic value coding for taste and other senses. In Aim #1, we will use in vivo neurophysiology and optogenetic circuit mapping in anesthetized mice to systematically study the sensitivity of parabrachial neurons to gustatory stimulation of the oral cavity and nociceptive stimulation of body extremities supplied by spinal afferents. Parabrachial neurons will be evaluated for projections to the amygdala, which is associated with emotional affect. Central interactions between taste and spinal somatosensory stimuli will also be studied. Moreover, we will address how inhibitory input from the amygdala influences taste and somatosensory sensitivity in parabrachial taste-integrative cells. Finally, studies in this Aim will use optical tagging of a genetic type of parabrachial neuron involved with aversive and protective behaviors to determine if gustatory-integrative parabrachial neurons are these cells. Aim #2 will use reversible silencing of this genetic cell class during measurement of taste-guided behaviors to determine the role of this parabrachial neuron type in innate gustatory preferences. Overall, these studies aim to elucidate novel neural circuit and genetic features of gustatory-active parabrachial neurons that pertain to their function and role in sensory valence processing. Resulting data will also bear on how taste sensations may interact with and modulate pain-related signals in the CNS.