Abstract
Purpose :
Damage to retinal ganglion cell axons alters conveyance of retinal signaling to visual areas of the brain and homeostatic processes are likely to trigger functional changes in neurons receiving retinal input. The goal of this study was to determine how loss of retinal inputs alters the function of thalamocortical (TC) relay neurons in the mouse dorsal lateral geniculate nucleus (dLGN), a major retinorecipient region of the brain.
Methods :
Mice (C57BL/6J) were bilaterally enucleated at 6-8 weeks of age. At several time points following enucleation (2-4 days, 7-10 days, and 2+ weeks), we prepared coronal brain slices (250 µm) using protected recovery method and targeted TC neurons for whole-cell patch clamp recording to monitor spontaneous synaptic inputs and passive and active membrane properties.
Results :
We observed an increasing trend in the number of spikes compared to controls (n = 6) for the same current injection after 2-4 days post enucleation (e.g. no. of spikes fired at 100 pA injection was statistically significant at p = 0.007, n = 9 for 7-10 days post enucleation and n = 5 for over 2 weeks post enucleation). The half maximal current for controls was 137.8 pA which increased to 200.8 pA after 2-4 days post enucleation and reduced to 89.34 pA and 91.95 pA 7-10 days post enucleation and after 2 weeks of enucleation respectively. Neither resting membrane potential (p = 0.716) nor input resistance were altered (p = 0.296). Miniature EPSC (mEPSC) frequency was identical to controls (n = 7) after 7-10 days of enucleation (n = 4) and we observed a decline in the mEPSC frequency after 2 weeks, but the difference was not significant (p = 0.073).
Conclusions :
Our results indicate that after 2-4 days of bilateral enucleation, the TC neurons become more excitable, without any detectable changes in passive membrane properties. Changes in neuronal excitability might represent a homeostatic attempt by TC neurons to compensate for loss of retinal input.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.