An excitatory ventromedial hypothalamus to paraventricular thalamus circuit that suppresses food intake

Nat Commun. 2020 Dec 10;11(1):6326. doi: 10.1038/s41467-020-20093-4.

Abstract

It is well recognized that ventromedial hypothalamus (VMH) serves as a satiety center in the brain. However, the feeding circuit for the VMH regulation of food intake remains to be defined. Here, we combine fiber photometry, chemo/optogenetics, virus-assisted retrograde tracing, ChR2-assisted circuit mapping and behavioral assays to show that selective activation of VMH neurons expressing steroidogenic factor 1 (SF1) rapidly inhibits food intake, VMH SF1 neurons project dense fibers to the paraventricular thalamus (PVT), selective chemo/optogenetic stimulation of the PVT-projecting SF1 neurons or their projections to the PVT inhibits food intake, and chemical genetic inactivation of PVT neurons diminishes SF1 neural inhibition of feeding. We also find that activation of SF1 neurons or their projections to the PVT elicits a flavor aversive effect, and selective optogenetic stimulation of ChR2-expressing SF1 projections to the PVT elicits direct excitatory postsynaptic currents. Together, our data reveal a neural circuit from VMH to PVT that inhibits food intake.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Designer Drugs / pharmacology
  • Energy Metabolism / drug effects
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology*
  • Glucose Tolerance Test
  • Integrases / metabolism
  • Leptin / pharmacology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Inhibition / drug effects
  • Neural Pathways / drug effects
  • Neural Pathways / physiology*
  • Neurons / drug effects
  • Neurons / physiology
  • Thalamus / drug effects
  • Thalamus / physiology*
  • Ventromedial Hypothalamic Nucleus / drug effects
  • Ventromedial Hypothalamic Nucleus / physiology*

Substances

  • Designer Drugs
  • Leptin
  • Cre recombinase
  • Integrases