A Light-Responsive Neural Circuit Suppresses Feeding

Overview

Journal J Neurosci

Specialty Neurology

Date 2024 Jun 19

PMID 38897723

Authors

Hailan Liu

Na Qu

Natalia Valdez Gonzalez

Marco A Palma

Huamin Chen

Jiani Xiong

Abhinav Choubey

Yongxiang Li

Xin Li

Meng Yu

Hesong Liu

Longlong Tu

Nan Zhang

Na Yin

Kristine Marie Conde

Mengjie Wang

Jonathan Carter Bean

Junying Han

Nikolas Anthony Scarcelli

Yongjie Yang

Kenji Saito

Huxing Cui

Qingchun Tong

Zheng Sun

Chunmei Wang

Xing Cai

Li Lu

Yang He

Yong Xu

Affiliations

Soon will be listed here.

Abstract

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb→5-HT circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light-responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice.

Citing Articles

The brainstem reticular formation pivots abnormal neural transmission in the course of Anorexia Nervosa.

Lazzeri G, Busceti C, Polzella A, Frati A, Puglisi-Allegra S, Fornai F J Neural Transm (Vienna). 2025; 132(4):547-565.

PMID: 39853374 DOI: 10.1007/s00702-025-02881-8.

References

OKane M, Wiles P, Wales J . Fluoxetine in the treatment of obese type 2 diabetic patients. Diabet Med. 1994; 11(1):105-10. DOI: 10.1111/j.1464-5491.1994.tb00238.x. View

Regmi P, Young M, Minigo G, Milic N, Gyawali P . Photoperiod and metabolic health: evidence, mechanism, and implications. Metabolism. 2023; 152:155770. DOI: 10.1016/j.metabol.2023.155770. View

Geisler S, Trimble M . The lateral habenula: no longer neglected. CNS Spectr. 2008; 13(6):484-9. DOI: 10.1017/s1092852900016710. View

He Y, Brouwers B, Liu H, Liu H, Lawler K, Mendes de Oliveira E . Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior. Nat Med. 2022; 28(12):2537-2546. PMC: 9800280. DOI: 10.1038/s41591-022-02106-5. View

Olsen M, Choi M, Kulseng B, Zhao C, Chen D . Time-restricted feeding on weekdays restricts weight gain: A study using rat models of high-fat diet-induced obesity. Physiol Behav. 2017; 173:298-304. DOI: 10.1016/j.physbeh.2017.02.032. View

He Y, Liu H, Yin N, Yang Y, Wang C, Yu M . Barbadin Potentiates Long-Term Effects of Lorcaserin on POMC Neurons and Weight Loss. J Neurosci. 2021; 41(26):5734-5746. PMC: 8244968. DOI: 10.1523/JNEUROSCI.3210-20.2021. View

Hattar S, Kumar M, Park A, Tong P, Tung J, Yau K . Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J Comp Neurol. 2006; 497(3):326-49. PMC: 2885916. DOI: 10.1002/cne.20970. View

Burke L, Heisler L . 5-hydroxytryptamine medications for the treatment of obesity. J Neuroendocrinol. 2015; 27(6):389-98. DOI: 10.1111/jne.12287. View

Huang L, Xi Y, Peng Y, Yang Y, Huang X, Fu Y . A Visual Circuit Related to Habenula Underlies the Antidepressive Effects of Light Therapy. Neuron. 2019; 102(1):128-142.e8. DOI: 10.1016/j.neuron.2019.01.037. View

10.

Okaty B, Freret M, Rood B, Brust R, Hennessy M, deBairos D . Multi-Scale Molecular Deconstruction of the Serotonin Neuron System. Neuron. 2015; 88(4):774-91. PMC: 4809055. DOI: 10.1016/j.neuron.2015.10.007. View

11.

Zhang Z, Beier C, Weil T, Hattar S . The retinal ipRGC-preoptic circuit mediates the acute effect of light on sleep. Nat Commun. 2021; 12(1):5115. PMC: 8387462. DOI: 10.1038/s41467-021-25378-w. View

12.

He Y, Cai X, Liu H, Conde K, Xu P, Li Y . 5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding. Mol Psychiatry. 2021; 26(12):7211-7224. PMC: 8776930. DOI: 10.1038/s41380-021-01220-z. View

13.

Sakhi K, Belle M, Gossan N, Delagrange P, Piggins H . Daily variation in the electrophysiological activity of mouse medial habenula neurones. J Physiol. 2013; 592(4):587-603. PMC: 3934703. DOI: 10.1113/jphysiol.2013.263319. View

14.

Lu X, Shieh K, Kabbaj M, Barsh G, Akil H, Watson S . Diurnal rhythm of agouti-related protein and its relation to corticosterone and food intake. Endocrinology. 2002; 143(10):3905-15. DOI: 10.1210/en.2002-220150. View

15.

Breisch S, Zemlan F, Hoebel B . Hyperphagia and obesity following serotonin depletion by intraventricular p-chlorophenylalanine. Science. 1976; 192(4237):382-5. DOI: 10.1126/science.130678. View

16.

Borniger J, Maurya S, Periasamy M, Nelson R . Acute dim light at night increases body mass, alters metabolism, and shifts core body temperature circadian rhythms. Chronobiol Int. 2014; 31(8):917-25. DOI: 10.3109/07420528.2014.926911. View

17.

LeGates T, Fernandez D, Hattar S . Light as a central modulator of circadian rhythms, sleep and affect. Nat Rev Neurosci. 2014; 15(7):443-54. PMC: 4254760. DOI: 10.1038/nrn3743. View

18.

Jeong J, Lee D, Kang S . Effects of chronic restraint stress on body weight, food intake, and hypothalamic gene expressions in mice. Endocrinol Metab (Seoul). 2014; 28(4):288-96. PMC: 3871039. DOI: 10.3803/EnM.2013.28.4.288. View

19.

Aklan I, Atasoy N, Yavuz Y, Ates T, Coban I, Koksalar F . NTS Catecholamine Neurons Mediate Hypoglycemic Hunger via Medial Hypothalamic Feeding Pathways. Cell Metab. 2019; 31(2):313-326.e5. PMC: 9017597. DOI: 10.1016/j.cmet.2019.11.016. View

20.

Saller C, Stricker E . Hyperphagia and increased growth in rats after intraventricular injection of 5,7-dihydroxytryptamine. Science. 1976; 192(4237):385-7. DOI: 10.1126/science.1257774. View