Figure 1. ‘Matched’ and ‘silent synapse’ models for E/I coordination in the DS circuit.

A. Schematic of the ‘matched’ model for DS. High-sensitivity (HS) bipolar cells (BCs) drive starbursts, while low-sensitivity (LS) BCs drive DSGCs (Poleg-Polsky and Diamond, 2016b). HS-BCs drive starbursts via AMPA receptors while the LS-BCs drive DSGCs using both AMPA and NMDA receptors. The starbursts, themselves, drive DSGCs via GABA_A and nicotinic Ach receptors (open arrows)

B. In the matched model, HS-BC inputs to starbursts are mediated by AMPA receptors. LS-BC input to DSGCs initiate precisely when starbursts reach their threshold for GABA/ ACh release. Thus, postsynaptic NMDA and non-NMDA (nACh/GABA/AMPA) receptor-mediated responses in DSGCs scale in proportion as a function of contrast (i.e. they are ‘matched’)

C. Multiplicative scaling: The matched model predicts that NMDA scales the DSGC spiking responses by a fixed fraction throughout its contrast range.

D. In the ‘silent synapse’ model to be tested here, common input provided by HS-BCs drive both starbursts and DSGCs (highlighted by the dashed circle). HS-BCs drive AMPA inputs in starbursts (black arrows), but NMDA-only inputs in DSGCs (grey arrows). Note, in both models presented (A, D) direction coding in DSGCs relies on asymmetric GABA release from starbursts (not depicted in the normalized contrast response functions).

E. In the silent synapse model, NMDA receptor-mediated inputs to DSGCs scale together with starburst inputs, while non-NMDA (ACh and AMPA) inputs initiate at a higher contrast. In this model, NMDA receptors are the only conductance activated in DSGCs at low-contrasts (shaded region). However, these NMDA receptors are silent until the DSGC receives non-NMDA inputs, a consequence of their voltage dependence (Sethuramanujam et al., 2016).

F. Additive scaling: The silent synapse model predicts that NMDA modulation of DSGC spiking would shift responses along the x-axis, increasing responses maximally in the middle of the contrast range.