Dataset Information

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

ABSTRACT:

Purpose

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.

Methods

In vivo electroporation was used to transiently express Cav ?1F or tamoxifen-inducible Cav ?1F in a subset of Cav1.4 knock-out mouse rods. Synaptogenesis was assayed using morphologic markers and a vision-guided water maze.

Results

We found that introduction of Cav ?1F to knock-out terminals rescued synaptic development as indicated by PSD-95 expression and elongated ribbons. When expression of Cav ?1F was induced in mature animals, we again found restoration of PSD-95 and elongated ribbons. However, the induced expression of Cav ?1F led to diffuse distribution of Cav ?1F 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.

Conclusions

These data confirm that Cav ?1F 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.

SUBMITTER: Laird JG

PROVIDER: S-EPMC6656410 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Laird Joseph G JG Gardner Sarah H SH Kopel Ariel J AJ Kerov Vasily V Lee Amy A Baker Sheila A SA

Investigative ophthalmology & visual science 20190701 8

<h4>Purpose</h4>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.<h4>Methods</h4>In vivo electroporation was used to t ...[more]

PMID: 31335952

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Dataset Information

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

Purpose

Methods

Results

Conclusions

Publications

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

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