Sustained microglia loss during development alters retinal ganglion cell firing during adulthood

The retina processes and transmits visual signals throughout a defined neuronal circuit to retinal ganglion cells, which project to the visual centers of the brain. Microglia have been shown to fine-tune the neuronal circuitry by pruning functionally weak synapses during brain development. However, we do not know whether microglia have a similar impact on the neuronal circuit of the retina.In mice, microglia invade the developing retina as early as embryonic age (E) 11.5, where they reside in in the emerging outer- (OPL) and inner plexiform layer (IPL) throughout adulthood. Here, we investigate the consequences of microglia loss during retinal development on retinal ganglion cell firing. For this, we exposed mice from E17.5 onwards to the CSF1-receptor inhibitor PLX5622, which depletes at least 50% of the microglia population. Then, we recorded the retinal ganglion cell activity upon light stimulation using a CMOS multi-electrode array in P30 animals. To investigate retinal ganglion cell activity upon light increments and decrements and direction selectivity, we use a full-field stimulus and a moving bar stimulus, respectively. Moreover, we employ a shifting white noise stimulus to examine the receptive field of retinal ganglion cells. Overall, our results indicate that loss of microglia during retinal development shifts the firing polarity of retinal ganglion cells towards less light ON and more light ON-OFF responses. Moreover, microglia loss resulted in larger receptive field center sizes compared to age matched control animals. These results suggest that microglia are involved in circuit formation and consequently signal processing in the retina.