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
-
- Animals
- CRISPR-Cas Systems
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Neurons*/metabolism
- Neurons*/physiology
- Relaxin/genetics
- Relaxin/metabolism
- Rhombencephalon/metabolism
- Rhombencephalon/physiology
- Zebrafish*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 38819436 Full text @ Elife
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:.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping