Spontaneous Depolarization-Induced Action Potentials of ON-Starburst Amacrine Cells during Cholinergic and Glutamatergic Retinal Waves.

Rong-Shan Yan,Dao-Qi Zhang,Xiong-Li Yang,Yong-Mei Zhong

doi:10.3390/cells9122574

Rong-Shan Yan, Dao-Qi Zhang + Show 2 more

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https://doi.org/10.3390/cells9122574

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Abstract

Correlated spontaneous activity in the developing retina (termed “retinal waves”) plays an instructive role in refining neural circuits of the visual system. Depolarizing (ON) and hyperpolarizing (OFF) starburst amacrine cells (SACs) initiate and propagate cholinergic retinal waves. Where cholinergic retinal waves stop, SACs are thought to be driven by glutamatergic retinal waves initiated by ON-bipolar cells. However, the properties and function of cholinergic and glutamatergic waves in ON- and OFF-SACs still remain poorly understood. In the present work, we performed whole-cell patch-clamp recordings and Ca2+ imaging from genetically labeled ON- and OFF-SACs in mouse flat-mount retinas. We found that both SAC subtypes exhibited spontaneous rhythmic depolarization during cholinergic and glutamatergic waves. Interestingly, ON-SACs had wave-induced action potentials (APs) in an age-dependent manner, but OFF-SACs did not. Simultaneous Ca2+ imaging and patch-clamp recordings demonstrated that, during a cholinergic wave, APs of an ON-SAC appeared to promote the dendritic release of acetylcholine onto neighboring ON- and OFF-SACs, which enhances their Ca2+ transients. These results advance the understanding of the cellular mechanisms underlying correlated spontaneous activity in the developing retina.

Highlights

Correlated spontaneous activity travels in a wave-like fashion (“retinal waves”) across the vertebrate retina before the emergence of vision [1,2]
Transgenic mice in which starburst amacrine cells (SACs) expressed a tdTomato fluorescent protein. tdTomatotdTomato-expressing cells were imaged from living retinas beginning at postnatal day 3 (P3) under fluorescent expressing cells were imaged from living retinas beginning at P3 under fluorescent microscopy
Our data demonstrate that ON- and OFF-SACs exhibited spontaneous rhythmic depolarization during cholinergic and glutamatergic waves, respectively

Summary

Introduction

Correlated spontaneous activity travels in a wave-like fashion (“retinal waves”) across the vertebrate retina before the emergence of vision [1,2]. Cholinergic retinal waves are initiated by and propagated between starburst amacrine cells (SACs), whereas glutamatergic retinal waves are generated by depolarizing (ON) bipolar cells [3,4,5] Both types of waves are transmitted vertically to retinal ganglion cells (RGCs), the output neurons of the retina, and propagate along the optic nerve to the brain. ON-SACs are readily accessible and have been studied extensively in the developing retinas of rodents, including rabbits and mice [3,12,13,14,15].

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