Abstract
Purpose: :
It was well documented that the spontaneous retinal activities, such as retinal waves, are critical for the maturation of RGC axonal projections in the LGN and genetic deletion of one subunit of TCR (CD3ζ) retarded the normal development of RGC axonal projections. The goal of this study is to determine whether TCR mediated signaling regulates the spontaneous retinal activity and whether different TCR subunits regulate different aspects of spontaneous retinal activity.
Methods: :
The glutamate receptor-mediated (stage III) spontaneous retinal waves were recorded as the spontaneous RGC action potentials using a multelectrode array (MEA) system from WT and several TCR subunits knockout mice (CD3-/-, CD4-/-, CD8-/- and Delta-/-) at the age of P10. Off-line Sorter was used to isolate the responses of individual neurons. Various aspects of retinal waves, such as wave duration, interwave interval, firing rate, correlation index, wave speed, wave size and wave strength (measured as the number of cells involved in each wave) were examined for each strain of mice by self-programmed software.
Results: :
Our results showed that all four TCR knockout strains showed prolonged wave duration from 13% (CD3-/-) to 56% (Delta-/-) increase in comparison with WT mice. However, other aspects of retinal waves were altered differently among different strains of TCR mutants. CD3-/- mice had a 6-fold increase of interwave interval while other 3 TCR knockout strains had minimum change in the interwave interval. The average firing rate of CD3-/- RGCs was only 27% of the WT but other 3 TCR knockout strains had 1.7- to 2.6-fold increase in the firing rate. In addition, the retinal waves in CD4-/-, CD8-/- and Delta-/- mice have 1.6- to 1.9-fold increase in wave size, 1.5- to 2-fold increase in wave strength and 1.2- to 1.5-fold increase in burst rate but 13% to 25% decrease in the propagation speed of the retinal wave in comparison with WT. On the other hand, CD3-/- mice had no significant difference in all of these wave properties in comparison with WT.
Conclusions: :
These results demonstrated that TCR-mediated signals regulate the spontaneous retinal activity during postnatal development. Since different subunits of TCRs seem to regulate different aspects of retinal spontaneous activity and alteration of spontaneous retinal activity could affect the maturation of synaptic circuits in both retina and higher center visual system, we concluded that these TCR mutants could provide valuable animal models for the study of the development of the synaptic pathways in the visual system.
Keywords: retina • retina: proximal (bipolar, amacrine, and ganglion cells) • retinal connections, networks, circuitry