Nat Commun. 2020 Dec 4;11(1):6218. doi: 10.1038/s41467-020-19980-7. | PubMed

B Sofia Beas¹, Xinglong Gu², Yan Leng¹, Omar Koita¹, Shakira Rodriguez-Gonzalez¹, Morgan Kindel¹, Bridget A Matikainen-Ankney³, Rylan S Larsen⁴, Alexxai V Kravitz^3,5, Mark A Hoon⁶, Mario A Penzo⁷

1. Unit on the Neurobiology of Affective Memory, National Institute of Mental Health, Bethesda, MD, USA.
2. Molecular Genetics Section, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA.
3. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
4. Allen Institute for Brain Science, Seattle, WA, USA.
5. Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
6. Molecular Genetics Section, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA. mark.hoon@nih.gov.
7. Unit on the Neurobiology of Affective Memory, National Institute of Mental Health, Bethesda, MD, USA. mario.penzo@nih.gov.

Abstract

Marked deficits in glucose availability, or glucoprivation, elicit organism-wide counter-regulatory responses whose purpose is to restore glucose homeostasis. However, while catecholamine neurons of the ventrolateral medulla (VLMCA) are thought to orchestrate these responses, the circuit and cellular mechanisms underlying specific counter-regulatory responses are largely unknown. Here, we combined anatomical, imaging, optogenetic and behavioral approaches to interrogate the circuit mechanisms by which VLMCA neurons orchestrate glucoprivation-induced food seeking behavior. Using these approaches, we found that VLMCA neurons form functional connections with nucleus accumbens (NAc)-projecting neurons of the posterior portion of the paraventricular nucleus of the thalamus (pPVT). Importantly, optogenetic manipulations revealed that while activation of VLMCA projections to the pPVT was sufficient to elicit robust feeding behavior in well fed mice, inhibition of VLMCA-pPVT communication significantly impaired glucoprivation-induced feeding while leaving other major counterregulatory responses intact. Collectively our findings identify the VLMCA-pPVT-NAc pathway as a previously-neglected node selectively controlling glucoprivation-induced food seeking. Moreover, by identifying the ventrolateral medulla as a direct source of metabolic information to the midline thalamus, our results support a growing body of literature on the role of the PVT in homeostatic regulation.

Presented By Sofia Beas