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

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

doi:10.1155/2018/2963232

Chieko Koike, Haruki Takeuchi + Show 8 more

Open Access

https://doi.org/10.1155/2018/2963232

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Abstract

TRPM1, the first member of the melanoma-related transient receptor potential (TRPM) subfamily, is the visual transduction channel downstream of metabotropic glutamate receptor 6 (mGluR6) on retinal ON bipolar cells (BCs). Human TRPM1 mutations are associated with congenital stationary night blindness (CSNB). In both TRPM1 and mGluR6 KO mouse retinas, OFF but not ON BCs respond to light stimulation. Here we report an unexpected difference between TRPM1 knockout (KO) and mGluR6 KO mouse retinas. We used a multielectrode array (MEA) to record spiking in retinal ganglion cells (RGCs). We found spontaneous oscillations in TRPM1 KO retinas, but not in mGluR6 KO retinas. We performed a structural analysis on the synaptic terminals of rod ON BCs. Intriguingly, rod ON BC terminals were significantly smaller in TRPM1 KO retinas than in mGluR6 KO retinas. These data suggest that a deficiency of TRPM1, but not of mGluR6, in rod ON bipolar cells may affect synaptic terminal maturation. We speculate that impaired signaling between rod BCs and AII amacrine cells (ACs) leads to spontaneous oscillations. TRPM1 and mGluR6 are both essential components in the signaling pathway from photoreceptors to ON BC dendrites, yet they differ in their effects on the BC terminal and postsynaptic circuitry.

Highlights

A fundamental feature of the early vertebrate visual system is the segregation of signals into ON and OFF pathways which separately signal increases and decreases in illumination, respectively
TRPM1 and metabotropic glutamate receptor 6 (mGluR6) cooperatively regulate the visual cascade in ON bipolar cells (BCs) and both are associated with congenital stationary night blindness (CSNB)
Example traces of firing during a 2-s light step were obtained from the wild type (WT), mGluR6

Summary

Introduction

A fundamental feature of the early vertebrate visual system is the segregation of signals into ON and OFF pathways which separately signal increases and decreases in illumination, respectively. These pathways originate in depolarizing ON bipolar cells (BCs) and hyperpolarizing OFF BCs, which respond with opposite polarity to light-evoked reductions in glutamate release from photoreceptors [1, 2]. All rod BCs are ON type, and cone. BCs are subdivided into ON and OFF types. The functional diversity of BCs results from the expression of different glutamate receptors (GluRs).

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