Correspondence between behavioural, physiological and anatomical measurements of visual function in inhibitory-neuron-ablated zebrafish

Jiaheng Xie, Patrick Goodbourn, Bang Viet Bui, Tamar Sztal, Patricia R. Jusuf

Research output: Contribution to journalArticleResearchpeer-review

Abstract

PURPOSE. To compare the effects of reduced inhibitory neuron function in the retina across
behavioral, physiological, and anatomical levels.
METHODS. Inhibitory neurons were ablated in larval zebrafish retina. The Ptf1a gene, which
determines inhibitory neuron fate in developing vertebrates, was used to express
nitroreductase. By exposing larvae to the prodrug metronidazole, cytotoxicity was selectively
induced in inhibitory neurons. Visual phenotypes were characterized at behavioral,
physiological, and anatomical levels using an optomotor response (OMR) assay, electroretinography (ERG), and routine histology, respectively. Nonvisual locomotion was also assessed
to reveal any general behavioral effects due to ablation of other nonvisual neurons that also
express Ptf1a.
RESULTS. Injured larvae showed severely reduced OMR relative to controls. Locomotor
assessment showed unaltered swimming ability, indicating that reduced OMR was due to
visual deficits. For ERG, injured larvae manifested either reduced (type-I) or absent (type-II) bwave signals originating from bipolar interneurons in the retina. Histologic analysis showed
altered retinal morphology in injured larvae, with reductions in synaptic inner plexiform layer
(IPL) thickness and synaptic density more pronounced in type-II than type-I larvae; type-II
larvae also had smaller retinae overall.
CONCLUSIONS. The consequences of inhibitory neuron ablation corresponded closely across
behavioral, physiological, and anatomical levels. Inhibitory neuron loss likely increases the
ratio of neural excitation to inhibition, leading to hyperexcitability. In addition to modulating
visual signals, inhibitory neurons may be critical for maintaining retinal structure and
organization. This study highlights the utility of a multidisciplinary approach and provides a template for characterizing other zebrafish models of neurological disease.
Original languageEnglish
Pages (from-to)4681-4690
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume60
Issue number14
DOIs
Publication statusPublished - 2019
Externally publishedYes

Keywords

  • retina
  • optomotor
  • electoretinography
  • analysis pipeline

Cite this

@article{a6621cf53181439ca0187e52d04e04e7,
title = "Correspondence between behavioural, physiological and anatomical measurements of visual function in inhibitory-neuron-ablated zebrafish",
abstract = "PURPOSE. To compare the effects of reduced inhibitory neuron function in the retina acrossbehavioral, physiological, and anatomical levels.METHODS. Inhibitory neurons were ablated in larval zebrafish retina. The Ptf1a gene, whichdetermines inhibitory neuron fate in developing vertebrates, was used to expressnitroreductase. By exposing larvae to the prodrug metronidazole, cytotoxicity was selectivelyinduced in inhibitory neurons. Visual phenotypes were characterized at behavioral,physiological, and anatomical levels using an optomotor response (OMR) assay, electroretinography (ERG), and routine histology, respectively. Nonvisual locomotion was also assessedto reveal any general behavioral effects due to ablation of other nonvisual neurons that alsoexpress Ptf1a.RESULTS. Injured larvae showed severely reduced OMR relative to controls. Locomotorassessment showed unaltered swimming ability, indicating that reduced OMR was due tovisual deficits. For ERG, injured larvae manifested either reduced (type-I) or absent (type-II) bwave signals originating from bipolar interneurons in the retina. Histologic analysis showedaltered retinal morphology in injured larvae, with reductions in synaptic inner plexiform layer(IPL) thickness and synaptic density more pronounced in type-II than type-I larvae; type-IIlarvae also had smaller retinae overall.CONCLUSIONS. The consequences of inhibitory neuron ablation corresponded closely acrossbehavioral, physiological, and anatomical levels. Inhibitory neuron loss likely increases theratio of neural excitation to inhibition, leading to hyperexcitability. In addition to modulatingvisual signals, inhibitory neurons may be critical for maintaining retinal structure andorganization. This study highlights the utility of a multidisciplinary approach and provides a template for characterizing other zebrafish models of neurological disease.",
keywords = "retina, optomotor, electoretinography, analysis pipeline",
author = "Jiaheng Xie and Patrick Goodbourn and Bui, {Bang Viet} and Tamar Sztal and Jusuf, {Patricia R.}",
year = "2019",
doi = "10.1167/iovs.19-27544",
language = "English",
volume = "60",
pages = "4681--4690",
journal = "Investigative Ophthalmology and Visual Science",
issn = "1552-5783",
publisher = "Association for Research in Vision and Ophthalmology",
number = "14",

}

Correspondence between behavioural, physiological and anatomical measurements of visual function in inhibitory-neuron-ablated zebrafish. / Xie, Jiaheng; Goodbourn, Patrick; Bui, Bang Viet; Sztal, Tamar; Jusuf, Patricia R.

In: Investigative Ophthalmology and Visual Science, Vol. 60, No. 14, 2019, p. 4681-4690.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Correspondence between behavioural, physiological and anatomical measurements of visual function in inhibitory-neuron-ablated zebrafish

AU - Xie, Jiaheng

AU - Goodbourn, Patrick

AU - Bui, Bang Viet

AU - Sztal, Tamar

AU - Jusuf, Patricia R.

PY - 2019

Y1 - 2019

N2 - PURPOSE. To compare the effects of reduced inhibitory neuron function in the retina acrossbehavioral, physiological, and anatomical levels.METHODS. Inhibitory neurons were ablated in larval zebrafish retina. The Ptf1a gene, whichdetermines inhibitory neuron fate in developing vertebrates, was used to expressnitroreductase. By exposing larvae to the prodrug metronidazole, cytotoxicity was selectivelyinduced in inhibitory neurons. Visual phenotypes were characterized at behavioral,physiological, and anatomical levels using an optomotor response (OMR) assay, electroretinography (ERG), and routine histology, respectively. Nonvisual locomotion was also assessedto reveal any general behavioral effects due to ablation of other nonvisual neurons that alsoexpress Ptf1a.RESULTS. Injured larvae showed severely reduced OMR relative to controls. Locomotorassessment showed unaltered swimming ability, indicating that reduced OMR was due tovisual deficits. For ERG, injured larvae manifested either reduced (type-I) or absent (type-II) bwave signals originating from bipolar interneurons in the retina. Histologic analysis showedaltered retinal morphology in injured larvae, with reductions in synaptic inner plexiform layer(IPL) thickness and synaptic density more pronounced in type-II than type-I larvae; type-IIlarvae also had smaller retinae overall.CONCLUSIONS. The consequences of inhibitory neuron ablation corresponded closely acrossbehavioral, physiological, and anatomical levels. Inhibitory neuron loss likely increases theratio of neural excitation to inhibition, leading to hyperexcitability. In addition to modulatingvisual signals, inhibitory neurons may be critical for maintaining retinal structure andorganization. This study highlights the utility of a multidisciplinary approach and provides a template for characterizing other zebrafish models of neurological disease.

AB - PURPOSE. To compare the effects of reduced inhibitory neuron function in the retina acrossbehavioral, physiological, and anatomical levels.METHODS. Inhibitory neurons were ablated in larval zebrafish retina. The Ptf1a gene, whichdetermines inhibitory neuron fate in developing vertebrates, was used to expressnitroreductase. By exposing larvae to the prodrug metronidazole, cytotoxicity was selectivelyinduced in inhibitory neurons. Visual phenotypes were characterized at behavioral,physiological, and anatomical levels using an optomotor response (OMR) assay, electroretinography (ERG), and routine histology, respectively. Nonvisual locomotion was also assessedto reveal any general behavioral effects due to ablation of other nonvisual neurons that alsoexpress Ptf1a.RESULTS. Injured larvae showed severely reduced OMR relative to controls. Locomotorassessment showed unaltered swimming ability, indicating that reduced OMR was due tovisual deficits. For ERG, injured larvae manifested either reduced (type-I) or absent (type-II) bwave signals originating from bipolar interneurons in the retina. Histologic analysis showedaltered retinal morphology in injured larvae, with reductions in synaptic inner plexiform layer(IPL) thickness and synaptic density more pronounced in type-II than type-I larvae; type-IIlarvae also had smaller retinae overall.CONCLUSIONS. The consequences of inhibitory neuron ablation corresponded closely acrossbehavioral, physiological, and anatomical levels. Inhibitory neuron loss likely increases theratio of neural excitation to inhibition, leading to hyperexcitability. In addition to modulatingvisual signals, inhibitory neurons may be critical for maintaining retinal structure andorganization. This study highlights the utility of a multidisciplinary approach and provides a template for characterizing other zebrafish models of neurological disease.

KW - retina

KW - optomotor

KW - electoretinography

KW - analysis pipeline

U2 - 10.1167/iovs.19-27544

DO - 10.1167/iovs.19-27544

M3 - Article

VL - 60

SP - 4681

EP - 4690

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 1552-5783

IS - 14

ER -