Optogenetic hedonic hotspots in orbitofrontal cortex and insula: causing enhancement of sweetness ‘liking’

Hedonic hotspots are localized brain sites where appropriate stimulations can amplify the hedonic impact of palatable tastes, measured as increases in affective orofacial ‘liking’ reactions to sweetness in rodents. Previously, two cortical hedonic hotspots in orbitofrontal cortex and insula were identified using opioid or orexin microinjections as neurochemical manipulations. Here we used optogenetic stimulation in male and female rats to independently confirm the sites and boundaries of two cortical hedonic hotspots, as well as their special hedonic enhancement functions. We report that channelrhodopsin stimulations within the two hedonic hotspots of rostral orbitofrontal and caudal insula each doubled the number of hedonic ‘liking’ reactions elicited by sucrose taste. Additionally, we confirmed that an intervening suppressive hedonic coldstrip stretches between them, where stimulation reduced ‘liking’ reactions. By contrast to the localization of hedonic hotspots for ‘liking’ enhancement, motivational ‘wanting’ for reward, measured as laser self-stimulation, was mediated by more widely distributed cortical sites in both hotspots and coldstrip. Significance Statement Orbitofrontal cortex and insula contain small 'hedonic hotspots' that increase 'liking' reactions to sweetness. Those hedonic hotspots were previously identified via local opioid/orexin microinjections, raising the danger they might be mere neurochemical artifacts of drug microinjections. We used optogenetic stimulation as an independent form of neuronal manipulation to assess whether they are instead robust neurobiological entities for hedonic enhancement. Our results confirm the OFC and insula ‘hotspots’ are robust hedonic entities: channelrhodopsin stimulation in rostromedial OFC or caudal insula hotspots enhanced ‘liking’. We also confirmed a suppressive 'hedonic coldstrip' spans between the two hotspots, where stimulation oppositely suppressed 'liking'. By contrast, motivational 'wanting' sites to seek reward were anatomically more widespread and included sites in the hedonic coldstrip and hotspots.