|ZFIN ID: ZDB-PUB-191115-7|
Correspondence Between Behavioral, Physiological, and Anatomical Measurements of Visual Function in Inhibitory Neuron-Ablated Zebrafish
Xie, J., Goodbourn, P.T., Bui, B.V., Sztal, T.E., Jusuf, P.R.
|Source:||Investigative ophthalmology & visual science 60: 4681-4690 (Journal)|
|Registered Authors:||Jusuf, Patricia, Sztal, Tamar Esther, Xie, Jiaheng|
|PubMed:||31725167 Full text @ Invest. Ophthalmol. Vis. Sci.|
Xie, J., Goodbourn, P.T., Bui, B.V., Sztal, T.E., Jusuf, P.R. (2019) Correspondence Between Behavioral, Physiological, and Anatomical Measurements of Visual Function in Inhibitory Neuron-Ablated Zebrafish. Investigative ophthalmology & visual science. 60:4681-4690.
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) b-wave 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.