Powerful effects on feeding are produced by manipulations of a number of neurotransmitter systems within the brain region known as the nucleus accumbens shell (AcbSh), suggesting that this part of the brain may play an important role in the control of food intake. The long-term goal of this research project is to identify and characterize the neural circuits through which the AcbSh produces changes in feeding behavior and to determine under what conditions the system controls food intake. The AcbSh appears to control activity in some neurons in another brain region known to mediate food intake, the lateral hypothalamus (LH). However, it is not yet known whether these two brain regions work together to control feeding behavior. The current proposal involves the use of a number of complementary neuroanatomical, behavioral, pharmacological, and molecular techniques to determine 1) whether neurons in the LH are necessary for the expression of AcbSh-mediated changes in feeding behavior and changes in activity in other brain regions, 2) whether LH neurons activated by AcbSh manipulations are connected to the medial hypothalamus or hindbrain and whether the brain peptide orexin, synthesized in some activated LH neurons, is necessary for the expression of AcbSh-mediated feeding, 3) whether AcbSh lesions disrupt spontaneous feeding and deprivation-induced food intake and brain activation in the circuit. The multidisciplinary nature of these studies will provide a rich and varied training experience for undergraduate and graduate students working on the project and successful completion of these studies will greatly clarify both the functional relationship between the AcbSh and lateral hypothalamus and the role of this circuit in the control of normal feeding behavior. In a more general sense, the project will provide data critical to advancing our understanding of the functional organization of the brain that will serve to guide neuroscientists in the investigation of other neural systems involved in the control of motivated behaviors.
