PittsburghV1, Main, Exploration, bibRecord, 000039

LRIT3 Differentially Affects Connectivity and Synaptic Transmission of Cones to ON- and OFF-Bipolar Cells

Identifieur interne : 000039 ( Main/Exploration ); précédent : 000038; suivant : 000040

LRIT3 Differentially Affects Connectivity and Synaptic Transmission of Cones to ON- and OFF-Bipolar Cells

Auteurs : Marion Neuillé [France] ; Yan Cao [États-Unis] ; Romain Caplette [France] ; Debbie Guerrero-Given [États-Unis] ; Connon Thomas [États-Unis] ; Naomi Kamasawa [États-Unis] ; José-Alain Sahel [France] ; Christian P. Hamel [France] ; Isabelle Audo [France] ; Serge Picaud [France] ; Kirill A. Martemyanov [États-Unis] ; Christina Zeitz [France]

Source :

Investigative Ophthalmology & Visual Science [ 0146-0404 ] ; 2017.

RBID : Hal:hal-01502294

English descriptors

mix :
- LRIT3, congenital stationary night blindness, electron microscopy, multielectrode array, retina.

Abstract

Purpose: Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). Using a cCSNB mouse model lacking Lrit3 (nob6), we recently have shown that LRIT3 has a role in the correct localization of TRPM1 (transient receptor potential melastatin 1) to the dendritic tips of ON-bipolar cells (BCs), contacting both rod and cone photoreceptors. Furthermore, postsynaptic clustering of other mGluR6 cascade components is selectively eliminated at the dendritic tips of cone ON-BCs. The purpose of this study was to further define the role of LRIT3 in structural and functional organization of cone synapses.Methods: Exhaustive electroretinogram analysis was performed in a patient with LRIT3 mutations. Multielectrode array recordings were performed at the level of retinal ganglion cells in nob6 mice. Targeting of GluR1 and GluR5 at the dendritic tips of OFF-BCs in nob6 retinas was assessed by immunostaining and confocal microscopy. The ultrastructure of photoreceptor synapses was evaluated by electron microscopy in nob6 mice.Results: The patient with LRIT3 mutations had a selective ON-BC dysfunction with relatively preserved OFF-BC responses. In nob6 mice, complete lack of ON-pathway function with robust, yet altered signaling processing in OFF-pathways was detected. Consistent with these observations, molecules essential for the OFF-BC signaling were normally targeted to the synapse. Finally, synaptic contacts made by ON-BC but not OFF-BC neurons with the cone pedicles were disorganized without ultrastructural alterations in cone terminals, horizontal cell processes, or synaptic ribbons.Conclusions: These results suggest that LRIT3 is likely involved in coordination of the transsynaptic communication between cones and ON-BCs during synapse formation and function.

Url:

http://hal.upmc.fr/hal-01502294

DOI: 10.1167/iovs.16-20745

Affiliations:

France, États-Unis

Links toward previous steps (curation, corpus...)

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Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en">LRIT3 Differentially Affects Connectivity and Synaptic Transmission of Cones to ON- and OFF-Bipolar Cells</title>
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<author><name sortKey="Picaud, Serge" sort="Picaud, Serge" uniqKey="Picaud S" first="Serge" last="Picaud">Serge Picaud</name>
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<author><name sortKey="Martemyanov, Kirill A" sort="Martemyanov, Kirill A" uniqKey="Martemyanov K" first="Kirill A." last="Martemyanov">Kirill A. Martemyanov</name>
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<author><name sortKey="Zeitz, Christina" sort="Zeitz, Christina" uniqKey="Zeitz C" first="Christina" last="Zeitz">Christina Zeitz</name>
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<idno type="DOI">10.1167/iovs.16-20745</idno>
<series><title level="j">Investigative Ophthalmology & Visual Science</title>
<idno type="ISSN">0146-0404</idno>
<imprint><date type="datePub">2017</date>
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<profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>LRIT3</term>
<term>congenital stationary night blindness</term>
<term>electron microscopy</term>
<term>multielectrode array</term>
<term>retina</term>
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<front><div type="abstract" xml:lang="en"> Purpose: Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). Using a cCSNB mouse model lacking Lrit3 (nob6), we recently have shown that LRIT3 has a role in the correct localization of TRPM1 (transient receptor potential melastatin 1) to the dendritic tips of ON-bipolar cells (BCs), contacting both rod and cone photoreceptors. Furthermore, postsynaptic clustering of other mGluR6 cascade components is selectively eliminated at the dendritic tips of cone ON-BCs. The purpose of this study was to further define the role of LRIT3 in structural and functional organization of cone synapses.Methods: Exhaustive electroretinogram analysis was performed in a patient with LRIT3 mutations. Multielectrode array recordings were performed at the level of retinal ganglion cells in nob6 mice. Targeting of GluR1 and GluR5 at the dendritic tips of OFF-BCs in nob6 retinas was assessed by immunostaining and confocal microscopy. The ultrastructure of photoreceptor synapses was evaluated by electron microscopy in nob6 mice.Results: The patient with LRIT3 mutations had a selective ON-BC dysfunction with relatively preserved OFF-BC responses. In nob6 mice, complete lack of ON-pathway function with robust, yet altered signaling processing in OFF-pathways was detected. Consistent with these observations, molecules essential for the OFF-BC signaling were normally targeted to the synapse. Finally, synaptic contacts made by ON-BC but not OFF-BC neurons with the cone pedicles were disorganized without ultrastructural alterations in cone terminals, horizontal cell processes, or synaptic ribbons.Conclusions: These results suggest that LRIT3 is likely involved in coordination of the transsynaptic communication between cones and ON-BCs during synapse formation and function. </div>
</front>
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LRIT3 Differentially Affects Connectivity and Synaptic Transmission of Cones to ON- and OFF-Bipolar Cells

LRIT3 Differentially Affects Connectivity and Synaptic Transmission of Cones to ON- and OFF-Bipolar Cells

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Abstract

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