Rescue of Rod Synapses by Induction of Cav Alpha 1F in the Mature Cav1.4 Knock-Out Mouse Retina

Joseph G Laird; Sarah H Gardner; Ariel J Kopel; Vasily Kerov; Amy Lee; Sheila A Baker

doi:10.1167/iovs.19-27226

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Rescue of Rod Synapses by Induction of Cav Alpha 1F in the Mature Cav1.4 Knock-Out Mouse Retina

Journal article

Open access

Peer reviewed

Rescue of Rod Synapses by Induction of Cav Alpha 1F in the Mature Cav1.4 Knock-Out Mouse Retina

Joseph G Laird, Sarah H Gardner, Ariel J Kopel, Vasily Kerov, Amy Lee and Sheila A Baker

Investigative ophthalmology & visual science, Vol.60(8), pp.3150-3161

07/01/2019

DOI: 10.1167/iovs.19-27226

PMCID: PMC6656410

PMID: 31335952

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Abstract

Cav1.4 is a voltage-gated calcium channel clustered at the presynaptic active zones of photoreceptors. Cav1.4 functions in communication by mediating the Ca2+ influx that triggers neurotransmitter release. It also aids in development since rod ribbon synapses do not form in Cav1.4 knock-out mice. Here we used a rescue strategy to investigate the ability of Cav1.4 to trigger synaptogenesis in both immature and mature mouse rods. In vivo electroporation was used to transiently express Cav α1F or tamoxifen-inducible Cav α1F in a subset of Cav1.4 knock-out mouse rods. Synaptogenesis was assayed using morphologic markers and a vision-guided water maze. We found that introduction of Cav α1F to knock-out terminals rescued synaptic development as indicated by PSD-95 expression and elongated ribbons. When expression of Cav α1F was induced in mature animals, we again found restoration of PSD-95 and elongated ribbons. However, the induced expression of Cav α1F led to diffuse distribution of Cav α1F in the terminal instead of being clustered beneath the ribbon. Approximately a quarter of treated animals passed the water maze test, suggesting the rescue of retinal signaling in these mice. These data confirm that Cav α1F expression is necessary for rod synaptic terminal development and demonstrate that rescue is robust even in adult animals with late stages of synaptic disease. The degree of rod synaptic plasticity seen here should be sufficient to support future vision-restoring treatments such as gene or cell replacement that will require photoreceptor synaptic rewiring.

Animals, Newborn

Immunohistochemistry

Synaptic Transmission - genetics

Mice, Inbred C57BL

Male

Retinal Rod Photoreceptor Cells - metabolism

Mice, Knockout

Animals

Calcium Channels, L-Type - genetics

Synapses - metabolism

Presynaptic Terminals - metabolism

Female

Models, Animal

Mice

Calcium Channels, L-Type - metabolism

Retinal Cone Photoreceptor Cells - metabolism

Details

Title: Subtitle: Rescue of Rod Synapses by Induction of Cav Alpha 1F in the Mature Cav1.4 Knock-Out Mouse Retina
Creators: Joseph G Laird - Department of Biochemistry, University of Iowa, Iowa City, United States
Sarah H Gardner - Department of Biochemistry, University of Iowa, Iowa City, United States
Ariel J Kopel - Department of Biochemistry, University of Iowa, Iowa City, United States
Vasily Kerov - Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
Amy Lee - Iowa Neuroscience Institute, University of Iowa, Iowa City, United States
Sheila A Baker - Ophthalmology and Visual Sciences and the Institute for Vision Research, University of Iowa, Iowa City, United States
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.60(8), pp.3150-3161
DOI: 10.1167/iovs.19-27226
PMID: 31335952
PMCID: PMC6656410
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: R01 EY026817 / NEI NIH HHS S10 RR025439 / NCRR NIH HHS R21 EY027054 / NEI NIH HHS
Language: English
Date published: 07/01/2019
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Biochemistry and Molecular Biology; University College Courses; Ophthalmology and Visual Sciences
Record Identifier: 9984070982002771

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