Wednesday, 4 October 2017: 09:10
National Harbor 11 (Gaylord National Resort and Convention Center)
Striatal dopamine plays key roles in modulating motor and reward behaviors. Dopamine release from striatal axons is often assumed to be governed exclusively by the firing pattern of midbrain dopamine neurons. However, it is also strongly influenced by local transmitters, especially acetylcholine (ACh), as well as extrinsic factors, like insulin. Indeed, ACh-dopamine interactions are central to the influence of peripherally derived insulin in the striatum. At physiological concentrations, insulin enhances evoked dopamine release in ex vivo striatal slices, monitored with fast-scan cyclic voltammetry (FSCV). This enhancement requires ACh and nAChRs, as the effect is lost in striatal slices from mice with forebrain ACh deletion, or after pharmacological antagonism of nAChRs. Consistent with these results, insulin also enhances evoked ACh release, detected using a carbon-fiber-based enzyme electrode to detect ACh. Further mplicating striatal cholinergic interneurons (ChIs) in this process, insulin ACh increases ChI excitability via insulin receptors on these cells. The amplification of DA release by insulin suggests a role for this neuropeptide as a reward signal, which complements its well-established role in satiety. Companion behavioral studies show that intact insulin signaling conveys the nutritive value of what we ingest, and thereby reinforces preference for high sugar substances. Together, these data reveal the key roles of local modulation of dopamine within the striatum in mediating the influence of insulin on motivation.