The conserved dopaminergic diencephalospinal tract mediates vertebrate locomotor development in zebrafish larvae
- Authors
- Lambert, A.M., Bonkowsky, J.L., and Masino, M.A.
- ID
- ZDB-PUB-121005-24
- Date
- 2012
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 32(39): 13488-13500 (Journal)
- Registered Authors
- Bonkowsky, Joshua
- Keywords
- none
- MeSH Terms
-
- Peripheral Nervous System Diseases/physiopathology
- N-Methylaspartate/pharmacology
- Locomotion/drug effects
- Locomotion/physiology*
- In Situ Nick-End Labeling
- Excitatory Amino Acid Agonists/pharmacology
- Dopamine/metabolism*
- Zebrafish Proteins/genetics
- Diencephalon/cytology
- Diencephalon/growth & development*
- Analysis of Variance
- Dopamine Agents/pharmacology
- Neurons/drug effects
- Neurons/metabolism
- Signal Transduction/drug effects
- Signal Transduction/genetics
- Transcription Factors/genetics
- Zebrafish
- Green Fluorescent Proteins/genetics
- Video Recording
- Animals
- Spinal Cord/growth & development*
- Nitroreductases/genetics
- Electrophysiology
- Neural Pathways/growth & development
- Neural Pathways/injuries
- Metronidazole/pharmacology
- Animals, Genetically Modified
- Larva
- Receptors, Dopamine D4/metabolism
- Dose-Response Relationship, Drug
- Peripheral Nerves/physiology
- PubMed
- 23015438 Full text @ J. Neurosci.
The most conserved part of the vertebrate dopaminergic system is the orthopedia (otp)-expressing diencephalic neuronal population that constitutes the dopaminergic diencephalospinal tract (DDT). Although studies in the neonatal murine spinal cord in vitro suggest an early locomotor role of the DDT, the function of the DDT in developing vertebrates in vivo remains unknown. Here, we investigated the role of the DDT in the locomotor development of zebrafish larvae. To assess the development of the behavioral and neural locomotor pattern, we used high-throughput video tracking in combination with peripheral nerve recordings. We found a behavioral and neural correspondence in the developmental switch from an immature to mature locomotor pattern. Blocking endogenous dopamine receptor 4 (D4R) signaling in vivo either before or after the developmental switch prevented or reversed the switch, respectively. Spinal transections of post-switch larvae reestablished the immature locomotor pattern, which was rescued to a mature-like pattern via spinal D4R agonism. Selective chemogenetic ablation of otp b (otpb) neurons that contribute to the DDT perpetuated the immature locomotor pattern in vivo. This phenotype was recapitulated by diencephalic transections that removed the dopaminergic otpb population and was rescued to a mature-like locomotor pattern by D4R agonism. We conclude that the dopaminergic otpb population, via the DDT, is responsible for spinal D4R signaling to mediate the developmental switch to the mature locomotor pattern of zebrafish. These results, integrated with the mammalian literature, suggest that the DDT represents an evolutionarily conserved neuromodulatory system that is necessary for normal vertebrate locomotor development.