Abstract
Purpose :
Most inner retinal neurons receive heightened rhythmic synaptic inputs following the degeneration of the rods and cones. We have previously shown that T-box transcription factor T-brain 2 (Tbr2) is expressed in all intrinsically photosensitive retinal ganglion cells and some displaced wide-field amacrine cells. The purpose here is to determine whether Tbr2-expressing neurons oscillate in the mouse Rd1 degeneration model and whether such information reflects synaptic connections of these neurons in a normal retina.
Methods :
We mated the Tbr2TauGFP-IRESCreERT2 mice (Chen et al., J. Comp. Neurol. 529:3513-32, 2021) into Rd1 and Ai9 backgrounds and delivered tamoxifen to label Tbr2-expressing neurons for targeted patch clamp recording. Morphology and electroretinography (ERG) were used to track the degree of photoreceptor degeneration. Light sensitivity of Tbr2-expressing WAC-1 and WAC-2 cells, identified by intrinsic membrane properties and dendritic morphology, were compared.
Results :
We found that M4 and M5 but not M1 ipRGCs oscillate following photoreceptor degeneration in the Rd1 mice. WAC-2 exhibits robust flupirtine-sensitive membrane oscillation, driven mainly by the gap junction network between AII-ACs and ON-cone bipolar cells. WAC-1 does not oscillate following photoreceptor degeneration, and in a normal retina, it responds only to mesopic and brighter light stimuli. In contrast, WAC-2 responds robustly to scotopic light stimuli in normal retinas.
Conclusions :
Comparing oscillation following retinal deafferentation and light sensitivity in normal retinas between Tbr2-expressing WAC-1 and WAC-2, we have demonstrated that neuronal oscillation in a deafferentated retina may reflect synaptic connections governing light sensitivity in a normal retina. Future studies will determine whether this applies to ipRGCs and other retinal neurons.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.