文章基本信息

标题：Local accumbens in vivo imaging during deep brain stimulation reveals a strategy-dependent amelioration of hedonic feeding
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作者：Hemmings Wu ; Bina Kakusa ; Sophie Neuner 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：1
DOI：10.1073/pnas.2109269118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance Impulsive overeating is a common, disabling feature of eating disorders. Calcium imaging using fiber photometry has emerged as an in vivo methodology to measure neuronal population activity immune to electrical stimulation artifact from deep brain stimulation (DBS). Thus, when used simultaneously, calcium imaging can elucidate poorly understood DBS mechanisms. We show that nucleus accumbens D1 medial spiny calcium signaling increases in preparation of hedonic feeding of high-fat food. Further, responsive, over continuous, DBS strategies effectively disrupt this activity leading to decreased consumption. Implementation of this methodology to better understand mechanisms of these and other forms of neuromodulation for various indications may help advance the field to identify novel therapeutic targets with applications extending beyond obesity. Impulsive overeating is a common, disabling feature of eating disorders. Both continuous deep brain stimulation (DBS) and responsive DBS, which limits current delivery to pathological brain states, have emerged as potential therapies. We used in vivo fiber photometry in wild-type, Drd1-cre, and A2a-cre mice to 1) assay subtype-specific medium spiny neuron (MSN) activity of the nucleus accumbens (NAc) during hedonic feeding of high-fat food, and 2) examine DBS strategy-specific effects on NAc activity. D1, but not D2, NAc GCaMP activity increased immediately prior to high-fat food approach. Responsive DBS triggered a GCaMP surge throughout the stimulation period and durably reduced high-fat intake. However, with continuous DBS, this surge decayed, and high-fat intake reemerged. Our results argue for a stimulation strategy-dependent modulation of D1 MSNs with a more sustained decrease in consumption with responsive DBS. This study illustrates the important role in vivo imaging can play in understanding effects of such novel therapies.
关键词：enresponsive neurostimulationdeep brain stimulationfiber photometryhedonic feedingnucleus accumbens