Rapid Eye Movement Sleep Engages Melanin-Concentrating Hormone Neurons to Reduce Cocaine Seeking

Guo, Rongqing; Wang, Yao; Yan, Rongzhen; Chen, Bin; Ding, Wanqiao; Gorczyca, Michael T.; Ozsoy, Sahin; Cai, Li; Hines, Rachel L.; Tseng, George C.; Allocca, Giancarlo; Dong, Yan; Fang, Jidong; Huang, Yanhua H.

doi:10.1016/j.biopsych.2022.06.006

Cited by 5 publications

(21 citation statements)

References 115 publications

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“…These changes may be independent of, but regulated by, MCH neuron activities, which in turn feed-back to REMS initiation and maintenance (8,21,54,55). Given the importance of MCH neuron activities and MCH signaling in regulating mood and drug seeking (10,22), these results provide a strong support to investigate EEG Ratio as a closely associated biometric in its potential for predicting future emotion and motivation-related behaviors. On the other hand, EEG Ratio features as biomarkers may exist independent of MCH neuron mechanisms.…”

Section: Discussionmentioning

confidence: 69%

“…AAV5-MCHp-GCaMP6f was constructed by connecting MCH promoter (MCHp) with GCaMP6f (Addgene #52925), packaged at University of North Carolina Vector Core, and diluted to ∼ 1-5×10 12 vg/ml working concentration. The expression specificity was validated previously (22).…”

Section: Methodsmentioning

confidence: 99%

“…Dual EEG and fiber photometry recordings were achieved through concentric configuration of the two recording cables, similar to previously described (22). Rats habituated in the recording chamber for 3 days after being tethered before recordings.…”

Section: Methodsmentioning

confidence: 99%

“…with feed-back control set to 31.5-34.5°C during ZT1-11 (10 h in the light period). Details see (22).…”

Section: Warmingmentioning

confidence: 99%

“…Thus, MCH neuron activities may provide important functional measures for sleep, emotion regulation, and drug relapse propensity. However, MCH neuron activities can only be monitored through invasive and low-throughput in vivo recordings combined with genetic labeling of these neurons (17, 18, 22, 23).…”

Section: Introductionmentioning

confidence: 99%

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An EEG Signature of MCH Neuron Activities Predicts Cocaine Seeking

Wang,

Li,

Widjaja

et al. 2024

Preprint

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Background: Identifying biomarkers that predict substance use disorder (SUD) propensity may better strategize anti-addiction treatment. The melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) critically mediates interactions between sleep and substance use; however, their activities are largely obscured in surface electroencephalogram (EEG) measures, hindering the development of biomarkers. Methods: Surface EEG signals and real-time Ca2+ activities of LH MCH neurons (Ca2+MCH) were simultaneously recorded in male and female adult rats. Mathematical modeling and machine learning were then applied to predict Ca2+MCH using EEG derivatives. The robustness of the predictions was tested across sex and treatment conditions. Finally, features extracted from the EEG-predicted Ca2+MCH either before or after cocaine experience were used to predict future drug-seeking behaviors. Results: An EEG waveform derivative - a modified theta-to-delta ratio (EEG Ratio) - accurately tracks real-time Ca2+MCH in rats. The prediction was robust during rapid eye movement sleep (REMS), persisted through REMS manipulations, wakefulness, circadian phases, and was consistent across sex. Moreover, cocaine self-administration and long-term withdrawal altered EEG Ratio suggesting shortening and circadian redistribution of synchronous MCH neuron activities. In addition, features of EEG Ratio indicative of prolonged synchronous MCH neuron activities predicted lower subsequent cocaine seeking. EEG Ratio also exhibited advantages over conventional REMS measures for the predictions. Conclusions: The identified EEG Ratio may serve as a non-invasive measure for assessing MCH neuron activities in vivo and evaluating REMS; it may also serve as a potential biomarker predicting drug use propensity.

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