Abstract
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 language | English |
|---|---|
| Pages (from-to) | 4681-4690 |
| Number of pages | 10 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 60 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - 2019 |
| Externally published | Yes |
Keywords
- retina
- optomotor
- electoretinography
- analysis pipeline
Cite this
}
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 journal › Article › Research › peer-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 -