Homotypic regulation of neuronal morphology and connectivity in the mouse retina.

The establishment of neuronal circuitry during development relies upon the action of cell-intrinsic mechanisms that specify neuronal form as well as plastic processes that require the transmission of neural activity between afferents and their targets. Here, we examine the role of interactions between neighboring like-type cells within the mouse retina upon neuronal differentiation and circuit formation. Two different genetically modified mouse models were used to modulate the density of homotypic neighbors, the Type 7 cone bipolar cells, without affecting the density of their afferents, the cone photoreceptors. We demonstrate a corresponding plasticity in dendritic field area when the density of Type 7 cone bipolar cells is elevated or reduced. In accord with this variation in dendritic field area across an invariant population of afferents, individual Type 7 cone bipolar cells are also shown to modulate the number of cone pedicles contacted without varying the number of contacts at each cone pedicle. Analysis of developing Type 7 cone bipolar cells reveals that the dendritic tiling present in maturity is achieved secondarily, after an initial stage of dendritic overlap, when the dendritic terminals are stratified at the level of the cone pedicles but are not localized to them. These results demonstrate a conspicuous developmental plasticity in neural circuit formation independent of neural activity, requiring homotypic interactions between neighboring cells that ultimately regulate connectivity within the retina.