Abstract
The lateral hypothalamus (LH) includes several anatomical subregions involved in eating and reward motivation. 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 subregion, the posterior LH subregion, and the lateral preoptic area. Local diameters of tissue optogenetically stimulated within the LH were assessed by measuring laser-induced Fos plumes and Jun plumes via immunofluorescence surrounding optic fiber tips. Those plume diameters were used to map localization of function for behavioral effects elicited by LH optogenetic stimulation. Optogenetic stimulation of the tuberal subsection of the LH produced the most robust eating behavior and 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, and at higher laser intensity shifted valence to evoke escape behaviors. We conclude that the tuberal LH subregion may best mediate stimulation-bound 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.
Highlights
The lateral hypothalamus (LH) has been considered a powerful regulator of food ingestion and reward-seeking motivation for over 60 years [1]
Intensities of Fos and Jun expression in each radial arm box were highly correlated together (r(80) = 0.771, p < 0.001), suggesting that both Fos and Jun plumes reflected similar underlying neuronal activation. This similarity helps give confidence that Fos or Jun plume intensities and diameters do accurately reflect the spread of optogenetic neuronal excitation induced in tissue surrounding an illuminated optic fiber tip
The sizes of Fos and Jun plumes were typically smaller than the extent of virus infection (0.3 mm average radius Fos/Jun plumes versus 0.5 mm average radius virus infection), suggesting that laser illumination neurobiologically excites only the proportion of infected neurons that are close enough to receive light intensity exceeding aCC-BY 4.0 International license
Summary
The lateral hypothalamus (LH) has been considered a powerful regulator of food ingestion and reward-seeking motivation for over 60 years [1]. Today the LH remains a prime target of research into obesity, anorexia, and reward-related motivational dysfunctions [2]. In early studies large LH lesions produced pathological excessive ‘disgust’, evident as gapes, headshakes and chin rubs that are normally elicited only by bitter or other unpalatable tastes, becoming elicited by the taste of sucrose [7,9,10]. Subsequent excitotoxin lesion studies showed that the site where neuron loss produced ‘disgust’ is in caudolateral ventral pallidum, anterior to LH, and not in LH itself [11,12]. LH lesions that do not damage the ventral pallidum, as well as neurotoxic destruction of dopamine fibers of passage through LH, do produce aphagia and sensory neglect, but not excessive ‘disgust’
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