title: Neuropeptidergic signaling partitions arousal behaviors in zebrafish.
abstract: Animals modulate their arousal state to ensure that their sensory responsiveness and locomotor activity match environmental demands. Neuropeptides can regulate arousal, but studies of their roles in vertebrates have been constrained by the vast array of neuropeptides and their pleiotropic effects. To overcome these limitations, we systematically dissected the neuropeptidergic modulation of arousal in larval zebrafish. We quantified spontaneous locomotor activity and responsiveness to sensory stimuli after genetically induced expression of seven evolutionarily conserved neuropeptides, including adenylate cyclase activating polypeptide 1b (adcyap1b), cocaine-related and amphetamine-related transcript (cart), cholecystokinin (cck), calcitonin gene-related peptide (cgrp), galanin, hypocretin, and nociceptin. Our study reveals that arousal behaviors are dissociable: neuropeptide expression uncoupled spontaneous activity from sensory responsiveness, and uncovered modality-specific effects upon sensory responsiveness. Principal components analysis and phenotypic clustering revealed both shared and divergent features of neuropeptidergic functions: hypocretin and cgrp stimulated spontaneous locomotor activity, whereas galanin and nociceptin attenuated these behaviors. In contrast, cart and adcyap1b enhanced sensory responsiveness yet had minimal impacts on spontaneous activity, and cck expression induced the opposite effects. Furthermore, hypocretin and nociceptin induced modality-specific differences in responsiveness to changes in illumination. Our study provides the first systematic and high-throughput analysis of neuropeptidergic modulation of arousal, demonstrates that arousal can be partitioned into independent behavioral components, and reveals novel and conserved functions of neuropeptides in regulating arousal.
authors.affiliation: Department of Biology, Ithaca College, Ithaca, New York 14850, and Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Woods
authors.forename: David
authors.initials: D
authors.lastname: Schoppik
authors.forename: Veronica J
authors.initials: VJ
authors.lastname: Shi
authors.forename: Steven
authors.initials: S
authors.lastname: Zimmerman
authors.forename: Haley A
authors.initials: HA
authors.lastname: Coleman
authors.forename: Joel
authors.initials: J
authors.lastname: Greenwood
authors.forename: Edward R
authors.initials: ER
authors.lastname: Soucy
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schier
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001143:Arousal / Q000235:genetics / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism; D003623:Dark Adaptation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D006358:Hot Temperature; D007814:Larva; D008027:Light; D008297:Male; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D018847:Opioid Peptides / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D025341:Principal Component Analysis; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D000097629:Nociceptin; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D015740:Calcitonin Gene-Related Peptide; D002766:Cholecystokinin; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018847:Opioid Peptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D029961:Zebrafish Proteins; D000097629:Nociceptin; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein