Genetic control of interconnected neuronal populations in the mouse primary visual system

Proliferation and survival of different cell types is thought to be modulated by cell interactions during development that achieve numerical and functional balance. We tested the precision of coregulation of numbers of neurons, glial cells, and endothelial cells in the dorsal lateral geniculate nucleus (LGN) in 58 isogenic strains of mice. We acquired matched counts of retinal ganglion cells (RGCs) in these strains and tested the precision of numerical matching between retina and LGN. Cells were counted using unbiased counting protocols and tissue from the Mouse Brain Library (www.mbl.org). Classification criteria were assessed using immunohistochemical criteria. The LGN contains an average of 17,000 neurons, 12,000 glial cells, and 10,000 endothelial cells. Variation around these means is typically twofold, and cell ratios vary widely. Strain differences in LGN volume correlate moderately well with glial cell number (r = 0.69) and less well with RGC number (r = 0.35) and with LGN neuron number (r = 0.32). Populations of LGN neurons and glial cells correlate only modestly (r = 0.44; p < 0.01). The single most surprising and unequivocal finding was the lack of any detectable correlation between populations of LGN neurons and RGCs, a correlation of merely 0.01 across 56 strains. In contrast, RGC number correlates significantly with LGN glial cell number, a surprising twist on the numerical matching hypothesis (r = 0.33; p < 0.01). We conclude that numbers of these two functionally coupled neuron populations are modulated over a wide range by independent genetic and developmental mechanisms.