The goals of the research proposed in this application are to study the neural circuitry and neurochemicals involved in positive and negative valence as measured by modulation of the acoustic startle reflex in rats. Our basis work in rodents on the circuitry of startle increased by negative valence, termed the fear-potentiated startle effect , has served as part of the basic science foundation in the CSEA for the study of startle modulation in humans. Thus far, however, our laboratory has not worked with positive valence in rats and how this might modulate startle amplitude. However, Dr. Michael Koch, one of the CSEA affiliate investigators, has now devised a method for quantifying positive valence measured as a decrease in startle amplitude when the reflex is elicited in the presence of a cue previously paired with food. He also has shown that dopamine in the nucleus accumbens is important for this pleasure-attenuated startle effect . This work now allows us to begin to use changes in rodent startle to delineate the circuitry involved in positive emotional valence similar to our work on the circuitry of negative emotional valence. Studies proposed in the current application will try to define in neural terms how negative valence leads to an elevation in startle amplitude and how positive valence leads to a decrease in startle amplitude. Double labeling studies will be used to determine whether different groups of cells in the basolateral amygdala project to the central nucleus of the amygdala vs. the nucleus accumbens. Retrograde tracing in combination with FOS-like immunocytochemistry will be used to determine whether cells in the basolateral amygdala that project to the central nucleus of the amygdala or cells in the central nucleus of the amygdala that project to the startle pathway are activated by lights paired with footshock, but not by lights paired with food. Similar studies will test whether cells in the basolateral amygdala that project to the nucleus accumbens are activated by lights paired with food, but not by lights paired with footshock. Based on recent data, we hypothesize that the intensity of both negative and positive valence, (i.e., the level of arousal) depends on the level of dopamine in either the amygdala or the nucleus accumbens during testing. Hence, we will also test the effects of local infusion of dopamine agonists into these brain regions on both fear-potentiated and pleasure-attenuated startle. Finally, we will test the effects of glutamate in the nucleus accumbens on both the acquisition and expression of pleasure- attenuated startle using local infusion of NMDA and AMPA agonists and antagonists in the nucleus accumbens and amygdala.
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