Inhibition is not required for the production of transient spiking responses from retinal ganglion cells

Ganglion cells responding only transiently to changes in illumination are f ound in many different vertebrate retinas. The interactions underlying form ation of these transient responses are still poorly understood. Two recentl y proposed hypotheses are (1) functional inhibitory pathways are necessary for transient response production, and (2) direct inhibition of the ganglio n cell has little effect on its output. Here, we examine these conclusions by using cell-attached patch-clamp recordings of spiking, whole-cell record ings of synaptic currents, and computer modeling. We found that picrotoxin (a GABA(A) and GABA(C) receptor antagonist), bicuculline (a GABA(A) recepto r antagonist), and strychnine (a glycine receptor antagonist), applied eith er singly or in combination, always failed to convert transient responses t o sustained responses. Application of the GABA(B) antagonist CGP35348 in th e presence of picrotoxin and strychnine also failed to convert transient re sponses into sustained responses. Whole-cell recordings of synaptic current s at various holding potentials indicated that direct inhibitory inputs to ganglion cells limit the duration of net excitation, implying that direct i nhibition does act to truncate the ganglion cell spiking response. Computer simulations using spiking and synaptic data from combined cell-attached an d whole-cell recordings supported this interpretation. We conclude that inh ibitory pathways are not required for generation of transient responses, bu t these pathways do serve to modulate transient ganglion cell spiking respo nses. We find that this modulation occurs, in part, via inhibitory inputs d irectly to the ganglion cell.