Whole-cell voltage clamp in the retinal slice and intracellular curren
t clamp in the intact retina were used to study inhibitory interaction
s in the inner plexiform layer. Picrotoxin or strychnine reduced inhib
itory, light-evoked currents in a majority of ganglion cells. However,
in nearly a third of the ganglion cells, each of these antagonists en
hanced the inhibitory synaptic current. All inhibitory current was blo
cked by the addition of the other antagonist. This indicates a cross-i
nhibition between GABAergic and glycinergic feedforward pathways. Bloc
king of GABA(A)Rs with SR95531 shortened the time course of both excit
atory and inhibitory synaptic currents in ganglion cells. Application
of picrotoxin, which blocked both GABA(A)Rs and GABA(C)Rs, produced th
e opposite effect. Recordings in the intact retina indicated that the
light responses of ON bipolar cells, sustained ON, and transient ON-OF
F third-order neurons were all made more transient by SR95531 and made
more sustained by picrotoxin. The data suggest that a GABA(C) feedbac
k pathway to bipolar cells makes light responses more phasic and that
this feedback is inhibited through a GABA(A)R pathway. Consequently, t
he balance between GABA(A)R and GABA(C)R inhibition regulates the time
course of inputs to ganglion cells.