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Brain-wide perception of the emotional valence of light is regulated by distinct hypothalamic neurons

Wagle, Mahendra and Zarei, Mahdi and Lovett-Barron, Matthew and Poston, Kristina Tyler and Xu, Jin and Ramey, Vince and Pollard, Katherine S. and Prober, David A. and Schulkin, Jay and Deisseroth, Karl and Guo, Su (2022) Brain-wide perception of the emotional valence of light is regulated by distinct hypothalamic neurons. Molecular Psychiatry . ISSN 1359-4184. doi:10.1038/s41380-022-01567-x. (In Press) https://resolver.caltech.edu/CaltechAUTHORS:20220428-551558200

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Abstract

Salient sensory stimuli are perceived by the brain, which guides both the timing and outcome of behaviors in a context-dependent manner. Light is such a stimulus, which is used in treating mood disorders often associated with a dysregulated hypothalamic-pituitary-adrenal stress axis. Relationships between the emotional valence of light and the hypothalamus, and how they interact to exert brain-wide impacts remain unclear. Employing larval zebrafish with analogous hypothalamic systems to mammals, we show in free-swimming animals that hypothalamic corticotropin releasing factor (CRF^(Hy)) neurons promote dark avoidance, and such role is not shared by other hypothalamic peptidergic neurons. Single-neuron projection analyses uncover processes extended by individual CRFᴴʸ neurons to multiple targets including sensorimotor and decision-making areas. In vivo calcium imaging uncovers a complex and heterogeneous response of individual CRFᴴʸ neurons to the light or dark stimulus, with a reduced overall sum of CRF neuronal activity in the presence of light. Brain-wide calcium imaging under alternating light/dark stimuli further identifies distinct and distributed photic response neuronal types. CRFᴴʸ neuronal ablation increases an overall representation of light in the brain and broadly enhances the functional connectivity associated with an exploratory brain state. These findings delineate brain-wide photic perception, uncover a previously unknown role of CRF^(Hy) neurons in regulating the perception and emotional valence of light, and suggest that light therapy may alleviate mood disorders through reducing an overall sum of CRF neuronal activity.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41380-022-01567-xDOIArticle
https://doi.org/10.1038/s41380-022-01647-yDOICorrection
https://github.com/Mahdizarei/Brain-wide-perception-of-the-emotional-valence-of-light-is-regulated-by-distinct-hypothalamic-neuronRelated ItemCode
ORCID:
AuthorORCID
Wagle, Mahendra0000-0003-1802-9330
Lovett-Barron, Matthew0000-0003-1425-5277
Poston, Kristina Tyler0000-0003-0957-8813
Xu, Jin0000-0002-5342-2341
Prober, David A.0000-0002-7371-4675
Schulkin, Jay0000-0002-1546-505X
Deisseroth, Karl0000-0001-9440-3967
Guo, Su0000-0002-7342-0108
Additional Information:© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Received 08 November 2021; Revised 25 February 2022; Accepted 06 April 2022; Published 28 April 2022. We thank our colleagues for sharing transgenic zebrafish lines: Misha Ahrens, Herwig Baier, Josh Bonkowsky, and Adam Douglass, as well as the Zebrafish International Resource Center (ZIRC). We thank Michael Munchua and Vivian Yuan for excellent fish care, and Guo lab members for helpful discussions. This work was supported by NIH R01 GM132500 (S.G.), NIH R35 NS122172 (D.A.P.), Gladstone Institutes (K.S.P.), NIH K99MH112840 (M.L.B.). Data availability: All primary data are stored on a secure server at the University of California, San Francisco and are available from the corresponding author. Code availability: Full coding implementation of all analysis tools are available at https://github.com/Mahdizarei/Brain-wide-perception-of-the-emotional-valence-of-light-is-regulated-by-distinct-hypothalamic-neuron. Contributions: MW and SG designed experiments. MW and KTP performed experiments. MW, MZ, and KTP analyzed data. MLB and KD contributed the electrophysiological data. JX and DP contributed the crhb CRISPR KO line. VR and KP performed bioinformatics analysis to identify crf enhancers. JS advised on the CRF system. MW, MZ, and SG wrote the paper with input from all authors. SG supervised all aspects of the work. The authors declare no competing interests.
Errata:Wagle, M., Zarei, M., Lovett-Barron, M. et al. Correction to: Brain-wide perception of the emotional valence of light is regulated by distinct hypothalamic neurons. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01647-y
Funders:
Funding AgencyGrant Number
NIHR01 GM132500
NIHR35 NS122172
Gladstone InstitutesUNSPECIFIED
NIHK99MH112840
Subject Keywords:Genetics; Neuroscience
DOI:10.1038/s41380-022-01567-x
Record Number:CaltechAUTHORS:20220428-551558200
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20220428-551558200
Official Citation:Wagle, M., Zarei, M., Lovett-Barron, M. et al. Brain-wide perception of the emotional valence of light is regulated by distinct hypothalamic neurons. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01567-x
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:114507
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:28 Apr 2022 20:15
Last Modified:30 Jun 2022 18:44

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