Internal States Influence the Representation and Modulation of Food Intake by Subthalamic Neurons

Abstract

Deep brain stimulation of the subthalamic nucleus (STN) is an effective therapy for motor deficits in Parkinson’s disease (PD), but commonly causes weight gain in late-phase PD patients probably by increasing feeding motivation. It is unclear how STN neurons represent and modulate feeding behavior in different internal states. In the present study, we found that feeding caused a robust activation of STN neurons in mice (GCaMP6 signal increased by 48.4% ± 7.2%, n = 9, P = 0.0003), and the extent varied with the size, valence, and palatability of food, but not with the repetition of feeding. Interestingly, energy deprivation increased the spontaneous firing rate (8.5 ± 1.5 Hz, n = 17, versus 4.7 ± 0.7 Hz, n = 18, P = 0.03) and the depolarization-induced spikes in STN neurons, as well as enhanced the STN responses to feeding. Optogenetic experiments revealed that stimulation and inhibition of STN neurons respectively reduced (by 11% ± 6%, n = 6, P = 0.02) and enhanced (by 36% ± 15%, n = 7, P = 0.03) food intake only in the dark phase. In conclusion, our results support the hypothesis that STN neurons are activated by feeding behavior, depending on energy homeostatic status and the palatability of food, and modulation of these neurons is sufficient to regulate food intake.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81701100, 81870891, and 81971038), the Fund for Jiangsu Province Specially-Appointed Professor (2016 and 2018), the Natural Science Foundation of Jiangsu Province, China (BK20171160), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (17KJA320007 and 18KJA320009), the Jiangsu Province Fund for Dominant Discipline (Anesthesiology), and Academic Startup Packages from Xuzhou Medical University, China (D2017009 and D2017010).

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Correspondence to Chunyi Zhou or Cheng Xiao.

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Wu, H., Yan, X., Tang, D. et al. Internal States Influence the Representation and Modulation of Food Intake by Subthalamic Neurons. Neurosci. Bull. (2020). https://doi.org/10.1007/s12264-020-00533-3

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Keywords

  • Subthalamic nucleus
  • Food intake
  • Fiber photometry
  • Optogenetics