Abstract
Purpose :
Glutamatergic retinal ganglion cells (RGCs) were thought to be the only projection neurons to the visual cortex. GABA is major inhibitory neurotransmitters that distributed widely in the retina. The projection and function of GABAergic RGCs remains unknown. In this research, we explore the potential function of GABAergic RGCs in the mouse retina.
Methods :
We use GAD2/vGAT-Cre transgenic mouse line combined with Cre-activated recombinant adeno-associated virus to trace the GABAergic RGCs circuitry. rAAV2/2-EF1a-DIO-EYFP and AAV2/retro-DIO-EYFP were injected in vitreous chamber or superior colliculus (SCs), respectively, to anterogradely or retrogradely label the GABAergic RGCs. Immunohistochemistry staining was used to identify the morphology and projection pattern of GABAergic RGCs. And the electrophysiological responses were explored by whole-cell recording. TaCaspase approach was used to ablate GABAergic RGCs and optomotor response (OMR), electroretinography (ERG) and looming test were performed to evaluate the visual function.
Results :
Anterogradely labeling showed that the main projection area of GABAergic RGCs were superficial superior colliculus (SCs) and the dorsal lateral geniculate nucleu (LGN). Retrogradely labeling from retino-recipient region SC indicated a sparse signal mainly distributed in the peripheral retina. About 3%-4% GABAergic RGCs showed co-localization with Brn3a, a specific RGCs marker. The distribution pattern showed no significant difference between vGAT and GAD2-cre mouse line. The SC-projecting GABAergic RGCs showed ON, OFF and ON-OFF responses to light in whole-cell recording which consistent to the dendrites distribution. We idenfitied at least ten subtypes RGCs according to mophological parameters, including soma size, dendritic stratification, dendritic field size. Ablating GABAergic RGCs by Caspase 3 showed dramatically defense response defect in looming test, whereas, have no influence in OMR, ERG response or intraocular pressure (IOP).
Conclusions :
These findings firstly report the projection of GABAergic RGCs to the visual cortex. And we systematically identified the morphological and function of GABAergic RGCs. Our results showed the critical role of GABAergic RGCs in defense response, and the important function in the retina.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.