The sense of taste plays a pivotal role in regulation of food intake and in determining the palatability of potential foodstuff. The overall goal of the proposed studies is to gain an understanding of the neurotransmitters and circuitry involved in regulation and processing of taste inputs within the primary taste nuclei of the brainstem. The primary taste nucleus in the brainstem of mammals, the nucleus of the solitary tract (NTS) is difficult to study because it contains numerous functional domains packed into a poorly differentiated, small structure. The proposed experiments take advantage of the distinct boundaries and laminated organization of the equivalent structure in a non-mammalian vertebrate. In this NTS equivalent, the vagal lobe, the primary gustatory afferents terminate in discrete layers, making the system amenable to both physiological and anatomical analyses that could not be carried out in other vertebrates. Glutamate, acting via both NMDA and non-NMDA ionotropic glutamate receptors, is the neurotransmitter of the primary gustatory afferents. The proposed experiments focus on early stage regulation of gustatory inputs by glutamate autoreceptors, ionotropic and metabotropic GABA receptors, and neuropeptides. Experiments in the first aim test whether glutamate autoreceptors situated on primary afferent terminals regulate synaptic transmission at the primary afferent terminals. We will utilize calcium imaging of an in vitro slice preparation to study the effects of ionotropic and metabotropic glutamate receptor agonists and antagonists on transmission by primary afferents. In addition, anatomical methods will be used to localize glutamate receptors in relation to the primary afferent terminals. The second aim relies on functional imaging and immunocytochemistry to determine whether GABA acts via presynaptic receptors to modulate primary gustatory inputs. In addition, we will define the GABAergic circuitry of the vagal lobe. The proposed experiments will determine mechanisms involved in regulation of transmission of primary gustatory input to the brainstem.