Different Activity Patterns in Retinal Ganglion Cells of TRPM1 and mGluR6 Knockout Mice

Takeuchi, Haruki; Horie, Sho; Moritoh, Satoru; Matsushima, Hiroki; Hori, Tesshu; Kimori, Yoshitaka; Kitano, Katsunori; Tsubo, Yasuhiro; Tachibana, Makoto; Koike, Chieko

doi:10.1155/2018/2963232

Cited by 19 publications

(21 citation statements)

References 32 publications

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“…The light-evoked Lrit3 -/-RGCs responses to light onset are similar to RGCs responses characterized in several CSNB1 mouse lines Nyx nob (Demas et al, 2006), Grm6 -/- (Rentería et al, 2006;Pinto et al, 2007;Peachey et al, 2017; Fig. 3), Trpm1 -/- (Takeuchi et al, 2018), and Lrit3 -/- (Fig. 3) and Lrit3 nob6 (Neuillé et al, 2017).…”

Section: Lrit3 Is Required For Both On and Off Pathway Signaling In Rgcssupporting

confidence: 76%

LRIT3 is Required for Nyctalopin Expression and Normal ON and OFF Pathway Signaling in the Retina

Hasan

Pangeni

Ray

et al. 2020

eNeuro

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The first retinal synapse, photoreceptor¡bipolar cell (BC), is both anatomically and functionally complex. Within the same synaptic region, a change in presynaptic glutamate release is sensed by both ON BCs (DBCs) via the metabotropic glutamate receptor 6 (mGluR6), and OFF BCs (HBCs) via ionotropic glutamate receptors to establish parallel signaling pathways that preferentially encode light increments (ON) or decrements (OFF), respectively. The synaptic structural organization of ON and OFF-type BCs at the photoreceptor terminal differs. DBCs make an invaginating synapse that contains a diverse but incompletely understood complex of interacting proteins (signalplex). HBCs make primarily flat contacts that contain an apparent different set of proteins that is equally uncharacterized. LRIT3 is a synaptic protein known to be essential for ON pathway visual function. In both male and female mice, we demonstrate that LRIT3 interacts with and is required for expression of nyctalopin, and thus TRPM1 at all DBC dendritic tips, but DBC signalplex components are not required for LRIT3 expression. Using whole-cell and multielectrode array (MEA) electrophysiology and glutamate imaging, we demonstrate that the loss of LRIT3 impacts both ON and OFF signaling pathway function. Without LRIT3, excitatory input to type 1 BCs is reduced, as are the visually evoked responses of many OFF retinal ganglion cells (RGCs). We conclude that the absence of LRIT3 expression disrupts excitatory input to OFF BCs and, thus disrupts the normal function of OFF RGCs.

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Section: Lrit3 Is Required For Both On and Off Pathway Signaling In Rgcssupporting

confidence: 76%

LRIT3 is Required for Nyctalopin Expression and Normal ON and OFF Pathway Signaling in the Retina

Hasan

Pangeni

Ray

et al. 2020

eNeuro

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“…Thresholds were reduced by approximately 10% and 30%, respectively, compared to WT [51]. While both mGluR6 and Trpm1 de cient mice lack ON BCs responses, spontaneous oscillatory ring in RGCs, the output cells of the retina, was only detected in Trpm1 −/− mice [10]. An attractive idea is that these retinal oscillations might be communicated along the optic nerve to higher visual centers and result in hyperlocomotion in Trpm1 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

“…We previously reported an unexpected difference between Trpm1 −/− and mGluR6 −/− mouse retinas. Spontaneous oscillations are observed in Trpm1 −/− retinas, but not in mGluR6 −/− retinas by recording spiking in retinal ganglion cells (RGCs) using a multielectrode array (MEA) [10]. We also previously reported that rod ON BC terminals were signi cantly smaller in Trpm1 −/− retinas than those of mGluR6 −/− [10].…”

Section: Introductionmentioning

confidence: 99%

“…Spontaneous oscillations are observed in Trpm1 −/− retinas, but not in mGluR6 −/− retinas by recording spiking in retinal ganglion cells (RGCs) using a multielectrode array (MEA) [10]. We also previously reported that rod ON BC terminals were signi cantly smaller in Trpm1 −/− retinas than those of mGluR6 −/− [10]. These data suggest that a de ciency of TRPM1, but not of mGluR6, in rod ON BCs may effect synaptic terminal maturation and could underlie the observed differences in oscillatory response.…”

Section: Introductionmentioning

confidence: 99%

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Mice with Mutations in Trpm1, a Gene within the locus of 15q13.3 Microdeletion Syndrome, Display Pronounced Hyperactivity and Decreased Anxiety-Like Behavior.

Hori

Ikuta

Takao

et al. 2020

Preprint

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15q13.3 microdeletion syndrome is a genetic disorder caused by a deletion of a region containing seven genes on chromosome 15, MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7, and characterized by a wide spectrum of psychiatric disorders. The contribution of each gene in this syndrome has been studied using mutant mouse models, but the phenotypes of these mice do not account for human phenotypes and the results are still controversial. The behavior of Trpm1−/− mice with relation to 15q13.3 microdeletion syndrome has not been investigated due to the visual impairment in these mice, which may confound the results of behavior tests that involve vision. We have now applied a comprehensive behavioral test battery to examine the relationship of TRPM1 and 15q13.3 microdeletion syndrome by using Trpm1 null mutant mice. Our data indicate abnormal behavior of Trpm1−/− mice which may explain some phenotypes of 15q13.3 microdeletion syndrome, including reduction of anxiety behavior, abnormality of social interaction, attenuation in fear memory, and hyperactivity, which is the most prominent phenotype of Trpm1 mutant mice. While the ON visual transduction pathway is impared in Trpm1−/− mice, we did not detect compensatory high sensitivities for other sensory modalities. Although Trpm1−/− mice share the same pathway for visual impairment with mGluR6−/− mice, hyperlocomotion activity has not been reported in mGluR6−/− mice. These data suggest that the phenotype of Trpm1−/− mice extends beyond that expected from visual impairment alone. This is the first evidence to associate TRPM1 with impairment of cognitive function similar to that found in the phenotypes of 15q13.3 microdeletion syndrome.

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“…This disruption in PNA expression, led us to examine dysfunction in OFF BC and RGC function in Lrit3 − mice. RGC response properties have been examined in several CSNB1 mouse lines (Nyx nob (Demas et al, 2006), Grm6 − / − (Renteria et al, 2006; Pinto et al, 2007; Peachey et al, 2017a), Trpm1 − / − (Takeuchi et al, 2018) and Lrit3 − / − (Fig. 4) and Lrit3 nob6 (Neuille et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

LRIT3 is required for nyctalopin expression and normal ON and OFF pathway signaling in the retina

Hasan

Pangeni

Ray

et al. 2018

Preprint

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37At its first synapse, the retina establishes two parallel channels that encode light increments (ON) or 38 decrements (OFF). At the same synapse, changes in photoreceptor glutamate release are sensed by 39 ON bipolar cells (BCs) via the metabotropic glutamate receptor 6 (mGluR6), and OFF BCs via 40 ionotropic BCs, which differ in their synaptic configuration with the photoreceptor terminal. ON BCs 41 form invaginating synapses that bring them in close proximity to presynaptic ribbons and the presumed 42 sole source of glutamate release. OFF bipolar cells form flat contacts distal to the ribbon synapse. We 43 investigated the role of LRIT3 in normal assembly and function of the mGlur6 signaling cascade 44 present in ON BCs. We demonstrate that LRIT3 is required for nyctalopin expression and thus TRPM1 45 expression and function. Using glutamate imaging, whole-cell electrophysiology, and multi-electrode 46 array extracellular recordings we demonstrate that the loss of LRIT3 impacts both the ON and OFF 47 128 129 Generation of Lrit3 -/mice with Zinc Finger Nucleases (ZFN) 130 131 C3H/HeNTac/C57BL/6NTac hybrid embryos (363) were injected with 10 ng/µl Lrit3 ZFN mRNA and 132 254 viable embryos were implanted into 9 Swiss Webster recipient mothers. Tail biopsies from offspring 133 were collected and genomic DNA isolated using Direct Tail PCR solution (Thermo Scientific) 134 supplemented with 0.2 μg/ml proteinase K (Thermo Scientific). Primers (5'-135

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Different Activity Patterns in Retinal Ganglion Cells of TRPM1 and mGluR6 Knockout Mice

Cited by 19 publications

References 32 publications

LRIT3 is Required for Nyctalopin Expression and Normal ON and OFF Pathway Signaling in the Retina

LRIT3 is Required for Nyctalopin Expression and Normal ON and OFF Pathway Signaling in the Retina

Mice with Mutations in Trpm1, a Gene within the locus of 15q13.3 Microdeletion Syndrome, Display Pronounced Hyperactivity and Decreased Anxiety-Like Behavior.

LRIT3 is required for nyctalopin expression and normal ON and OFF pathway signaling in the retina

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