Abstract
Purpose :
Brain-derived neurotrophic factor (BDNF) is a key regulator of nervous system plasticity with important roles in the development and maintenance. Within the visual system, the role of retinal BDNF transported to the dorsolateral geniculate nucleus (dLGN), the visual relay center of the thalamus, has not been characterized. Therefore, our goal was to determine whether retinal BDNF influences the development of the dLGN by selectively deleting retinal BDNF using Cre-lox technology.
Methods :
We used a mouse line with Cre expression specific to the retina (Chx10-Cre) crossed with BDNFfl/fl mice to selectively delete BDNF from the retina. To test for visual system function differences between Chx10-Cre;BDNFfl/fl (cKO) and control (C57Bl/6J or BDNFfl/fl mice) of both sexes, we analyzed eye tracking abilities in an optomotor (OMR) task using stimuli of varying spatial frequency (n=46) or contrast sensitivity (n=31) and recorded electroretinograms (ERGs) to analyze any retinal differences (n=26 eyes). We also analyzed mEPSCs (n=41) as well as sholl analysis (n=21) in neurobiotin-filled dLGN thalamocortical (TC) neurons. Additionally, we analyzed binocular segregation using intravitreally-injected cholera toxin b (CTb) traces in young mice (n=10).
Results :
Results from OMR showed that cKO mice spent less time tracking than controls (spatial frequency: p=0.02; cKO n = 24, ctr n = 22 mice, unpaired t-test; contrast sensitivity: p=0.02; cKO n = 18, ctr n = 13 mice, unpaired t-test), however, there were no differences in outer retinal light responses (p=0.7 A wave, p=0.9 B wave; cKO n = 10 eyes, ctr n = 16 eyes, unpaired t-test). cKO TC neurons had a higher frequency (p=0.02) and lower area in cKO mEPSCs (p=0.046), (cKO n = 19 cells, 9 mice; ctr n = 22 cells, 12 mice, nested t-test nested t-test). Sholl analysis of TC neurons indicated that cKO TC neurons were significantly less complex than control neurons (p=0.03, -7.183 ± 3.066 SEM; cKO n = 11 cells, 6 mice; ctr n = 10 cells, 4 mice). Additionally, CTb analysis suggested no significant differences in binocular segregation (p=0.97; cKO n = 5 mice; ctr n = 5 mice, unpaired t-test).
Conclusions :
These results suggest that retinal BDNF plays a role in the structure and function of the dLGN. These results further our understanding of both developmental and neurodegenerative processes in the visual system.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.