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 and Avishek Adhikari ()
Additional contact information
Fernando M. C. V. Reis: University of California, Los Angeles
Sandra Maesta-Pereira: University of California, Los Angeles
Matthias Ollivier: University of California, Los Angeles
Peter J. Schuette: University of California, Los Angeles
Ekayana Sethi: University of California, Los Angeles
Blake A. Miranda: University of California, Los Angeles
Emily Iniguez: University of California, Los Angeles
Meghmik Chakerian: University of California, Los Angeles
Eric Vaughn: Harvard University
Megha Sehgal: University of California, Los Angeles
Darren C. T. Nguyen: University of California, Los Angeles
Faith T. H. Yuan: University of California, Los Angeles
Anita Torossian: University of California, Los Angeles
Juliane M. Ikebara: Universidade Federal do ABC
Alexandre H. Kihara: Universidade Federal do ABC
Alcino J. Silva: University of California, Los Angeles
Jonathan C. Kao: University of California, Los Angeles
Baljit S. Khakh: University of California, Los Angeles
Avishek Adhikari: University of California, Los Angeles

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-46430-5

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