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Control of feeding by a bottom-up midbrain-subthalamic pathway

  • Fernando M. C. V. Reis,
  • Sandra Maesta-Pereira,
  • Matthias Ollivier,
  • Peter J. Schuette,
  • Ekayana Sethi,
  • Blake A. Miranda,
  • Emily Iniguez,
  • Meghmik Chakerian,
  • Eric Vaughn,
  • Megha Sehgal,
  • Darren C. T. Nguyen,
  • Faith T. H. Yuan,
  • Anita Torossian,
  • Juliane M. Ikebara,
  • Alexandre H. Kihara,
  • Alcino J. Silva,
  • Jonathan C. Kao,
  • Baljit S. Khakh,
  • Avishek Adhikari

摘要

Investigative exploration and foraging leading to food consumption have vital importance, but are not well-understood. Since GABAergic inputs to the lateral and ventrolateral periaqueductal gray (l/vlPAG) control such behaviors, we dissected the role of vgat-expressing GABAergic l/vlPAG cells in exploration, foraging and hunting. Here, we show that in mice vgat l/vlPAG cells encode approach to food and consumption of both live prey and non-prey foods. The activity of these cells is necessary and sufficient for inducing food-seeking leading to subsequent consumption. Activation of vgat l/vlPAG cells produces exploratory foraging and compulsive eating without altering defensive behaviors. Moreover, l/vlPAG vgat cells are bidirectionally interconnected to several feeding, exploration and investigation nodes, including the zona incerta. Remarkably, the vgat l/vlPAG projection to the zona incerta bidirectionally controls approach towards food leading to consumption. These data indicate the PAG is not only a final downstream target of top-down exploration and foraging-related inputs, but that it also influences these behaviors through a bottom-up pathway.