Intraspinal serotonergic signaling suppresses locomotor activity in larval zebrafish

Abstract

Serotonin (5HT) is a modulator of many vital processes in the spinal cord (SC), such as production of locomotion. In the larval zebrafish, intraspinal serotonergic neurons (ISNs) are a source of spinal 5HT that, despite the availability of numerous genetic and optical tools, has not yet been directly shown to affect the spinal locomotor network. In order to better understand the functions of ISNs, we used a combination of strategies to investigate ISN development, morphology, and function. ISNs were optically isolated from one another by photoconverting Kaede fluorescent protein in individual cells, permitting morphometric analysis as they developed in vivo. ISN neurite lengths and projection distances exhibited the greatest amount of change between 3 and 4 days post-fertilization (dpf) and appeared to stabilize by 5 dpf. Overall ISN innervation patterns were similar between cells and between SC regions. ISNs possessed rostrally-extending neurites resembling dendrites and a caudally-extending neurite resembling an axon, which terminated with an enlarged growth cone-like structure. Interestingly, these enlargements remained even after neurite extension had ceased. Functionally, application of exogenous 5HT reduced spinally-produced motor nerve bursting. A selective 5HT reuptake inhibitor and ISN activation with channelrhodopsin-2 each produced similar effects to 5HT, indicating that spinally-intrinsic 5HT originating from the ISNs has an inhibitory effect on the spinal locomotor network. Taken together this suggests that the ISNs are morphologically mature by 5 dpf and supports their involvement in modulating the activity of the spinal locomotor network. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018.

Comparative effects of mercury chloride and methylmercury exposure on early neurodevelopment in zebrafish larvae

“…45 Intraspinal serotonergic signaling suppresses locomotor activity in larval zebrash and chemogenetic ablation of dopaminergic neurons leads to transient locomotor impairments in zebrash larvae. 46,47 Putrescine, niacinamide, uric acid, and squalene all can induce oxidative stress, which may cause apoptosis and nerve damage. 13,48 But in HgCl 2 group, putrescine, niacinamide, uric acid was observed changed, whereas squalene in MeHgCl.…”

Serotonin in Animal Cognition and Behavior

“…Central 5-HT is also a powerful neuromodulator of locomotor activities in various vertebrates, including lamprey [82], zebrafish [83][84][85], Xenopus [86,87], and rodents (mouse, rat, rabbit; [88][89][90]. In spinal rats and mice, serotonergic agonists are amongst the most powerful drugs promoting the activation of the sub-lesional locomotor networks and the recovery of locomotor movements following a spinal cord injury [91][92][93].…”

Serotonergic Modulation of Locomotor Activity From Basal Vertebrates to Mammals

“…In the isolated spinal cord of zebrafish, optogenetic activation of Pet1-positive 5-HT neurons/fibers decreases the number of fictive locomotor bursts, an effect similar to that evoked by SSRI and exogenous 5-HT in the same preparation (Montgomery et al, 2018). It remains to be determined whether these effects involve only intraspinal 5-HT neurons and/or descending raphe 5-HT fibers that may still be able to release 5-HT in the isolated spinal cord (Montgomery et al, 2018).…”