Optogenetic mapping of feeding and self-stimulation within the lateral hypothalamus of the rat

Abstract

The lateral hypothalamus (LH) regulates eating and motivation, and includes several anatomical subregions. This study explored localization of function across different LH subregions in controlling food intake stimulated by optogenetic channelrhodopsin excitation, and in supporting laser self-stimulation. We particularly compared the tuberal LH, the posterior LH, and the lateral preoptic area. Local diameters of tissue optogenetically stimulated within LH were assessed by measuring laser-induced Fos plumes and Jun plumes via immunofluorescence surrounding optic fiber tips, and were used to map localization of function for effects elicited by LH optogenetic stimulation. Optogenetic stimulation of the tuberal subsection of the LH behaviorally produced the most robust food intake initially, but produced only mild laser self-stimulation in the same rats. However, after repeated exposures to optogenetic stimulation, tuberal LH behavioral profiles shifted toward more self-stimulation and less food intake. By contrast, stimulation of the lateral preoptic area produced relatively little food intake or self-stimulation, either initially or after extended stimulation experience. Stimulation in the posterior LH subregion supported moderate self-stimulation, but not food intake here, and at higher laser intensity shifted valence to evoke escape behaviors. We conclude that the tuberal LH subregion may best mediate increases in food intake stimulated by optogenetic excitation. However, incentive motivational effects of tuberal LH stimulation may shift toward self-stimulation behavior after repeated stimulation. By contrast, the lateral preoptic area and posterior LH do not as readily elicit either eating behavior or laser self-stimulation, and may be more prone to higher-intensity aversive effects.