Dataset Information

Firing dynamics and modulatory actions of supraspinal dopaminergic neurons during zebrafish locomotor behavior.

ABSTRACT:

Background

Dopamine (DA) has long been known to have modulatory effects on vertebrate motor circuits. However, the types of information encoded by supraspinal DAergic neurons and their relationship to motor behavior remain unknown.

Results

By conducting electrophysiological recordings from awake, paralyzed zebrafish larvae that can produce behaviorally relevant activity patterns, we show that supraspinal DAergic neurons generate two forms of output: tonic spiking and phasic bursting. Using paired supraspinal DA neuron and motoneuron recordings, we further show that these firing modes are associated with specific behavioral states. Tonic spiking is prevalent during periods of inactivity while bursting strongly correlates with locomotor output. Targeted laser ablation of supraspinal DA neurons reduces motor episode frequency without affecting basic parameters of motor output, strongly suggesting that these cells regulate spinal network excitability.

Conclusions

Our findings reveal how vertebrate motor circuit flexibility is temporally controlled by supraspinal DAergic pathways and provide important insights into the functional significance of this evolutionarily conserved cell population.

SUBMITTER: Jay M

PROVIDER: S-EPMC4331284 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Publications

Firing dynamics and modulatory actions of supraspinal dopaminergic neurons during zebrafish locomotor behavior.

Jay Michael M De Faveri Francesca F McDearmid Jonathan Robert JR

Current biology : CB 20150129 4

<h4>Background</h4>Dopamine (DA) has long been known to have modulatory effects on vertebrate motor circuits. However, the types of information encoded by supraspinal DAergic neurons and their relationship to motor behavior remain unknown.<h4>Results</h4>By conducting electrophysiological recordings from awake, paralyzed zebrafish larvae that can produce behaviorally relevant activity patterns, we show that supraspinal DAergic neurons generate two forms of output: tonic spiking and phasic bursti ...[more]

PMID: 25639243

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Project description:Recessive mutations in the F-box only protein 7 gene (FBXO7) cause PARK15, a mendelian form of early-onset, levodopa-responsive parkinsonism with severe loss of nigrostriatal dopaminergic neurons. However, the function of the protein encoded by FBXO7, and the pathogenesis of PARK15 remain unknown. No animal models of this disease exist. Here, we report the generation of a vertebrate model of PARK15 in zebrafish. We first show that the zebrafish Fbxo7 homolog protein (zFbxo7) is expressed abundantly in the normal zebrafish brain. Next, we used two zFbxo7-specific morpholinos (targeting protein translation and mRNA splicing, respectively), to knock down the zFbxo7 expression. The injection of either of these zFbxo7-specific morpholinos in the fish embryos induced a marked decrease in the zFbxo7 protein expression, and a range of developmental defects. Furthermore, whole-mount in situ mRNA hybridization showed abnormal patterning and significant decrease in the number of diencephalic tyrosine hydroxylase-expressing neurons, corresponding to the human nigrostriatal or ventral tegmental dopaminergic neurons. Of note, the number of the dopamine transporter-expressing neurons was much more severely depleted, suggesting dopaminergic dysfunctions earlier and larger than those due to neuronal loss. Last, the zFbxo7 morphants displayed severe locomotor disturbances (bradykinesia), which were dramatically improved by the dopaminergic agonist apomorphine. The severity of these morphological and behavioral abnormalities correlated with the severity of zFbxo7 protein deficiency. Moreover, the effects of the co-injection of zFbxo7- and p53-specific morpholinos were similar to those obtained with zFbxo7-specific morpholinos alone, supporting further the contention that the observed phenotypes were specifically due to the knock down of zFbxo7. In conclusion, this novel vertebrate model reproduces pathologic and behavioral hallmarks of human parkinsonism (dopaminergic neuronal loss and dopamine-dependent bradykinesia), representing therefore a valid tool for investigating the mechanisms of selective dopaminergic neuronal death, and screening for modifier genes and therapeutic compounds.

Dataset Information

Firing dynamics and modulatory actions of supraspinal dopaminergic neurons during zebrafish locomotor behavior.

Background

Results

Conclusions

Publications

Firing dynamics and modulatory actions of supraspinal dopaminergic neurons during zebrafish locomotor behavior.

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