PUBLICATION

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

Authors
Wagle, M., Zarei, M., Lovett-Barron, M., Poston, K.T., Xu, J., Ramey, V., Pollard, K.S., Prober, D.A., Schulkin, J., Deisseroth, K., Guo, S.
ID
ZDB-PUB-220430-2
Date
2022
Source
Molecular psychiatry   27(9): 3777-3793 (Journal)
Registered Authors
Guo, Su, Prober, David, Wagle, Mahendra
Keywords
none
MeSH Terms
  • Perception
  • Calcium
  • Mammals/metabolism
  • Brain/metabolism
  • Animals
  • Hypothalamus/metabolism
  • Neurons/metabolism
  • Corticotropin-Releasing Hormone*/metabolism
  • Paraventricular Hypothalamic Nucleus*/metabolism
  • Zebrafish/metabolism
(all 10)
PubMed
35484242 Full text @ Mol. Psychiatry
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 (CRFHy) 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 CRFHy 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.
Genes / Markers
Figures
Figure Gallery (7 images)
Show all Figures
Expression
Phenotype
Fish Conditions Stage Phenotype Figure
ABchemical treatment by environment: antalarminDays 7-13
crhbct862/ct862standard conditionsDays 7-13
jf5Tg/jf5Tg; rw0144Tg/rw0144Tg; s2510Tg/s2510Tgaltered light dark cycleDay 6
jf5Tg/jf5Tg; rw0144Tg/rw0144Tg; s2510Tg/s2510Tgaltered light dark cycleDay 6
jf5Tg/jf5Tg; rw0144Tg/rw0144Tg; s2510Tg/s2510Tgaltered light dark cycle, chemical treatment by environment: metronidazoleDay 6
jf5Tg/jf5Tg; rw0144Tg/rw0144Tg; s2510Tg/s2510Tgaltered light dark cycle, chemical treatment by environment: metronidazoleDay 6
jf5Tg/jf5Tg; rw0144Tg/rw0144Tg; s2510Tg/s2510Tgaltered light dark cycle, chemical treatment by environment: metronidazoleDay 6
jf5Tg/jf5Tg; rw0144Tg/rw0144Tg; s2510Tg/s2510Tgaltered light dark cycle, chemical treatment by environment: metronidazoleDay 6
jf5Tg/jf5Tg; rw0144Tg/rw0144Tg; s2510Tg/s2510Tgaltered light dark cycle, chemical treatment by environment: metronidazoleDay 6
jf5Tg/jf5Tg; rw0144Tg/rw0144Tg; s2510Tg/s2510Tgaltered light dark cycle, chemical treatment by environment: metronidazoleDay 6
1 - 10 of 40
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ct862
    Indel
    jf5TgTransgenic Insertion
      mpn134TgTransgenic Insertion
        mpn219TgTransgenic Insertion
          nns19TgTransgenic Insertion
            rw0144TgTransgenic Insertion
              s2510TgTransgenic Insertion
                s2511TgTransgenic Insertion
                  zc57TgTransgenic Insertion
                    zf3181TgTransgenic Insertion
                      1 - 10 of 10
                      Show
                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab2-serotoninpolyclonal
                        IgGRabbit
                        Ab4-thpolyclonalRabbit
                        1 - 2 of 2
                        Show
                        Orthology
                        No data available
                        Engineered Foreign Genes
                        Marker Marker Type Name
                        GAL4EFGGAL4
                        GAL4FFEFGGAL4FF
                        GCaMPEFGGCaMP
                        GFPEFGGFP
                        mCherryEFGmCherry
                        1 - 5 of 5
                        Show
                        Mapping
                        No data available