We propose to establish microdialysis in the awake, behaving preparation as a technique for investigating amino acid transmitters and neuropeptides in the gustatory-responsive (rostral) nucleus of the solitary tract (rNST). Although microdialysis has been used in many regions of the CNS with great success, the potential of this technique has remained unexploited in the gustatory system. Salt deprivation, hunger, satiety and conditioned aversions have all been demonstrated to impact neural responsiveness in the gustatory system. The neural basis for these state-dependent changes is unknown, but, based on their role in other sensory systems, a predominant role for peptide neuromodulators, perhaps acting via interneurons utilizing excitatory or inhibitory amino acids, is a compelling hypothesis. Understanding the functional neurochemistry of gustatory processing would be greatly facilitated by the ability to monitor the release of multiple neuroactive agents in an animal actively engaged in gustatory-driven behavior. Microdialysis can meet these requirements. The present studies will provide a foundation for assessing this hypothesis by establishing the capabilities of microdialysis followed by HPLC and electrochemical detection in the first-order gustatory relay. The first experiments will monitor amino acid release in an anesthetized preparation, in which precisely controlled taste stimulation is possible. The results of these experiments will be critical in interpreting data obtained in a second series of studies which will apply microdialysis to monitor amino acid release in an awake preparation. A third series of studies will develop microdialysis for assessing the release of multiple neuropeptides, by adapting electrochemical detection techniques to this purpose. When the proposed studies are brought to fruition, future work will be directed at examining the neurochemical basis for fluctuations in gustatory sensitivity as a function of metabolic or nutritional status, and as a function of learning or task demands. The characterization of the dynamic neurochemistry associated with gustatory processing under varying homeostatic conditions offers therapeutic avenues to either increase food intake in response to cachexia or to limit intake for obesity.
