PUBLICATION

Genetically defined nucleus incertus neurons differ in connectivity and function

Authors
Spikol, E.D., Cheng, J., Macurak, M., Subedi, A., Halpern, M.E.
ID
ZDB-PUB-240601-1
Date
2024
Source
eLIFE   12: (Journal)
Registered Authors
Cheng, Ji, Halpern, Marnie E., Macurak, Michelle, Spikol, Emma, Subedi, Abhi
Keywords
CRISPR knock-in, behavior, hindbrain, neural circuits, neuroscience, nucleus incertus, relaxin-3, zebrafish
MeSH Terms
  • Rhombencephalon/metabolism
  • Rhombencephalon/physiology
  • CRISPR-Cas Systems
  • Animals
  • Relaxin/genetics
  • Relaxin/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish*
  • Neurons*/metabolism
  • Neurons*/physiology
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
(all 13)
PubMed
38819436 Full text @ Elife
Abstract
The nucleus incertus (NI), a conserved hindbrain structure implicated in the stress response, arousal, and memory, is a major site for production of the neuropeptide relaxin-3. On the basis of goosecoid homeobox 2 (gsc2) expression, we identified a neuronal cluster that lies adjacent to relaxin 3a (rln3a) neurons in the zebrafish analogue of the NI. To delineate the characteristics of the gsc2 and rln3a NI neurons, we used CRISPR/Cas9 targeted integration to drive gene expression specifically in each neuronal group, and found that they differ in their efferent and afferent connectivity, spontaneous activity, and functional properties. gsc2 and rln3a NI neurons have widely divergent projection patterns and innervate distinct subregions of the midbrain interpeduncular nucleus (IPN). Whereas gsc2 neurons are activated more robustly by electric shock, rln3a neurons exhibit spontaneous fluctuations in calcium signaling and regulate locomotor activity. Our findings define heterogeneous neurons in the NI and provide new tools to probe its diverse functions.
Genes / Markers
Figures
Figure Gallery (16 images) / 2
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
c264TgTransgenic Insertion
    c375TgTransgenic Insertion
      c426TgTransgenic Insertion
        c591TgTransgenic Insertion
          c631TgTransgenic Insertion
            c636TgTransgenic Insertion
              c682TgTransgenic Insertion
                c718TgTransgenic Insertion
                  c836TgTransgenic Insertion
                    c578TgTransgenic Insertion
                      1 - 10 of 17
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      gsc2CRISPR1-gsc2CRISPR
                      rln3aCRISPR1-rln3aCRISPR
                      1 - 2 of 2
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                      Fish
                      Antibodies
                      No data available
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CFPEFGCFP
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GAL4FFEFGGAL4FF
                      GCaMPEFGGCaMP
                      GFPEFGGFP
                      mAppleEFGmApple
                      mCherryEFGmCherry
                      NTREFGNTR
                      QFEFGQF
                      1 - 10 of 13
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                      Mapping
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                      Citation
                      Spikol, E.D., Cheng, J., Macurak, M., Subedi, A., Halpern, M.E. (2024) Genetically defined nucleus incertus neurons differ in connectivity and function. eLIFE. 12:.