Intersecting Circuits Generate Precisely Patterned Retinal Waves

The developing retina generates spontaneous glutamatergic (stage III) waves of activity that sequentially recruit neighboring ganglion cells with opposite light responses (ON and OFF RGCs). This activity pattern is thought to help establish parallel ON and OFF pathways in downstream visual areas. The circuits that produce stage III waves and desynchronize ON and OFF RGC firing remain obscure. Using dual patch-clamp recordings, we find that ON and OFF RGCs receive sequential excitatory input from ON and OFF cone bipolar cells (CBCs), respectively. This input sequence is generated by crossover circuits, in which ON CBCs control glutamate release from OFF CBCs via diffusely stratified inhibitory amacrine cells. In addition, neighboring ON CBCs communicate directly and indirectly through lateral glutamatergic transmission and gap junctions, both of which are required for wave initiation and propagation. Thus, intersecting lateral excitatory and vertical inhibitory circuits give rise to precisely patterned stage III retinal waves. •Asynchronous excitation sequentially recruits ON and OFF RGCs into stage III waves•ON CBCs control and delay glutamate release from OFF CBCs via inhibitory diffuse ACs•ON CBCs are excited by lateral glutamatergic transmission and gap junctions•Intersecting orthogonal inhibitory and excitatory circuits generate stage III waves The developing retina generates spontaneous patterns of activity (i.e., retinal waves) that shape the connectivity of the emerging visual system. Akrouh and Kerschensteiner describe that intersecting lateral excitatory and vertical inhibitory circuits generate glutamatergic waves of activity in the retina.