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

Jia Zhang,Dan Chen,Yunlei Yang,Patrick Sweeney

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.

Highlights

It is well recognized that ventromedial hypothalamus (VMH) serves as a satiety center in the brain
To test whether VMH steroidogenic factor 1 (SF1) neurons are under the control of hunger states, we first performed dual-wavelength fiber photometry (FP) to monitor calcium levels of VMH SF1 neurons in freely moving SF1-Cre mice, which were transduced with genetically encoded Ca2+ indicator GCaMP6f in SF1 neurons and implanted with an optic fiber on the surface of VMH (Fig. 1a–c)
We observed that the intensity of SF1 neuron Ca2+ signals was stronger in the early light period (ELP; 09:00–11:00) than in the late light period (LLP; 18:00–20:00), opposite to the amount of food intake (Fig. 1d)

Summary

Introduction

It is well recognized that ventromedial hypothalamus (VMH) serves as a satiety center in the brain. Two recent studies indicate that activation of VMH neurons modulates food intake[22,23]; the neural circuitry governing VMH suppression of food intake remains to be deciphered. In this present study, we performed a series of experiments to decipher the downstream target that partakes in the VMH suppression of food intake. We found that activation of SF1 neuronal projections to the PVT or the PVT-projecting SF1 neurons reduced food intake; inactivation of PVT neurons diminished the SF1 suppression of feeding; and our ChR2-assisted circuit mapping experiments demonstrated direct synaptic projections from VMH SF1 neurons to the neurons in the PVT. Our results reveal an anorexigenic neural circuit that inhibits food intake

Methods

Results

Conclusion