In contrast to the activity-regulated refinement of stratified On and Off RGCs, the segregated ingrowth of On- and Off-cone bipolar cells occurs in a highly specific manner, and is not dependent on the presence of either RGCs or cholinergic amacrine cells. It is suggested that the directed ingrowth of bipolar cell axons is guided by molecular cues expressed in the extracellular matrix whose identity is yet to be established.
There is also evidence that the later formation of segregated On and Off retinogeniculate projections in the ferret is regulated by an activity-dependent Hebbian type mechanism. Blockade of RGC discharges as well as NMDA receptors in the dlgn perturbs the formation of such segregated inputs. Moreover, On and Off RGCs show distinct correlated firing patterns during the developmental period when the intermingled projections of these neurons are being sorted into sign specific sublayers.
Collectively, the available evidence indicates that different developmental mechanisms operate on the different components of retinal and retinogeniculate On and Off pathways to attain the segregated state characteristic of the mature visual system.
A Precisely Timed Asynchronous Pattern of ON and OFF Retinal Ganglion Cell Activity during Propagation of Retinal Waves