PUBLICATION

Norepinephrine is required to promote wakefulness and for hypocretin-induced arousal in zebrafish

Authors

Singh, C., Oikonomou, G., Prober, D.A.

ID

ZDB-PUB-150917-6

Date

2015

Source

eLIFE 4: e07000 (Journal)

Registered Authors

Prober, David

Keywords

hypocretin, neuroscience, norepinephrine, sleep, zebrafish

MeSH Terms

Animals
Dopamine beta-Hydroxylase/deficiency
Dopamine beta-Hydroxylase/genetics
Dopamine beta-Hydroxylase/metabolism
Norepinephrine/deficiency
Norepinephrine/metabolism*
Autonomic Nervous System Diseases
Wakefulness/drug effects*
Arousal/drug effects*
Orexins/metabolism*
Zebrafish/genetics
Zebrafish/physiology*

(all 12)

PubMed

26374985 Full text @ Elife

Abstract

Pharmacological studies in mammals suggest that norepinephrine (NE) plays an important role in promoting arousal. However, the role of endogenous NE is unclear, with contradicting reports concerning the sleep phenotypes of mice lacking NE due to mutation of dopamine β-hydroxylase (dbh). To investigate NE function in an alternative vertebrate model, we generated dbh mutant zebrafish. In contrast to mice, these animals exhibit dramatically increased sleep. Surprisingly, despite an increase in sleep,dbh mutant zebrafish have a reduced arousal threshold. These phenotypes are also observed in zebrafish treated with small molecules that inhibit NE signaling, suggesting that they are caused by the lack of NE. Using genetic overexpression of hypocretin (Hcrt) and optogenetic activation of hcrt-expressing neurons, we also find that NE is important for Hcrt-induced arousal. These results establish a role for endogenous NE in promoting arousal and indicate that NE is a critical downstream effector of Hcrt neurons.

Genes / Markers

Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by environment: prazosin hydrochloride	Day 5 to Day 6	locomotory behavior decreased process quality, abnormal	Fig. 1
WT	chemical treatment by environment: prazosin hydrochloride	Day 5 to Day 6	sleep increased duration, abnormal	Fig. 1
WT	chemical treatment by environment: prazosin hydrochloride	Day 5 to Day 6	sleep increased occurrence, abnormal	Fig. 1
ct831Tg	visible light	Day 5	locomotory behavior increased process quality, abnormal	Fig. 6
ct831Tg	visible light	Day 5	locomotory behavior increased process quality, abnormal	Fig. 8
ct831Tg/ct831Tg	visible light	Day 5	locomotory behavior increased process quality, abnormal	Fig. 5
dbh^ct806/+; zf12Tg	heat shock	Day 5 to Day 6	sleep decreased process quality, abnormal	Fig. 4
dbh^ct806/ct806	control	Day 5	locomotory behavior decreased process quality, abnormal	Fig. 8
dbh^ct806/ct806	standard conditions	Day 5 to Day 6	locomotory behavior decreased process quality, abnormal	Fig. 2
dbh^ct806/ct806	standard conditions	Day 5 to Day 6	sleep increased duration, abnormal	Fig. 2

1 - 10 of 14

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ct806		Insertion	dbh
ct819Tg	Tg(hcrt:RFP)	Transgenic Insertion
ct821Tg	Tg2(dbh:EGFP)	Transgenic Insertion
ct831Tg	Tg(hcrt:Cr.Chr2_H134R-EYFP)	Transgenic Insertion
hu2098		Point Mutation	hcrtr2
zf11Tg	Tg(-2.0Tru.Hcrt:EGFP)	Transgenic Insertion
zf12Tg	Tg(hsp70l:hcrt)	Transgenic Insertion

1 - 7 of 7

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
ct831Tg
ct831Tg/ct831Tg
dbh^ct806/ct806
dbh^ct806/ct806; ct831Tg
dbh^ct806/ct806; zf12Tg
dbh^ct806/+; zf12Tg
hcrtr2^{hu2098/hu2098}
hcrtr2^{hu2098/hu2098}; ct831Tg
WT
zf11Tg

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-hcrt	polyclonal			Rabbit

Orthology

Gene	Orthology
dbh

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
EYFP	EFG	EYFP
RFP	EFG	RFP

Mapping

Singh et al., 2015 ZDB-PUB-150917-6 PMID:26374985

Norepinephrine is required to promote wakefulness and for hypocretin-induced arousal in zebrafish

Singh et al., 2015

ZDB-PUB-150917-6
PMID:26374985