Intersecting Circuits Generate Precisely Patterned Retinal Waves

Abstract

SUMMARY 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.

GABAergic regulation of spontaneous spike patterns in the developing rabbit retina

“…It seems that the large propagating waves at stage II may be suited for global competition between ganglion cell projections from the two eyes and/or between ganglion cells from different retinal regions, while the diversely patterned local bursts at stage III may be useful in shaping synaptic connections and circuits of different ganglion cell types in a cell type-specific manner. Recent studies in mouse retina show that ON and OFF ganglion cells fire asynchronously during stage III retinal waves [2,9], consistent with a potential role of stage III waves in cell subtype-specific development.…”

“…Thus, our study suggests that the emergence of inhibition from amacrine cells plays an important role in shaping and regulating the diverse spike patterns of ganglion cells. On the other hand, because bipolar cells also participate in stage III waves [2,7], an additional possibility of a developmental GABAergic contribution at the outer plexiform layer cannot be excluded.…”

CaV3.2 KO mice have altered retinal waves but normal direction selectivity

“…First, several cell types in the circuit that mediate retinal waves – including bipolar cells, starburst amacrine cells and DSGCs – are depolarized during these waves (Zhou, 1998; Elstrott & Feller, 2010; Ford et al , 2012; Firl et al , 2013; Akrouh & Kerschensteiner, 2013). Thus they are robustly activated by spontaneous activity.…”

“…Glutamatergic waves are mediated by glutamate release from bipolar cells (Firl et al , 2013; Akrouh & Kerschensteiner, 2013), however which aspects of the circuit control burst properties and the frequency of waves are not yet identified. In the retina, T-type channels have been described in bipolar cell terminals and retinal ganglion cells (Ma & Pan, 2003; Pan et al , 2001; Lee et al , 2003; Hu et al , 2009; Cui et al , 2012; Sargoy et al , 2014).…”

“…A critical component of the network mediating waves and a primary source of depolarizing input to RGCs is glutamate release from bipolar cells (Firl et al , 2013; Akrouh & Kerschensteiner, 2013). In the adult retina, bipolar cells exhibit unstable membrane potentials and their spontaneous depolarizations are mediated by low-voltage activated T-type calcium channels (Ma & Pan, 2003; Cueni et al , 2009; Sargoy et al , 2014; Puthussery et al , 2014) that are expressed in subsets of bipolar cells (Pan et al , 2001; Singer & Diamond, 2003) and of ganglion cells (Sargoy et al , 2014).…”