Starburst amacrine cells (SBACs) within the adult mammalian retina provide the critical inhibition that underlies the receptive field properties of direction-selective ganglion cells (DSGCs). The SBACs generate direction-selective output of GABA that differentially inhibits the DSGCs. We review the biophysical mechanisms that produce directional GABA release from SBACs and test a network model that predicts the effects of reciprocal inhibition between adjacent SBACs. The results of the model simulations suggest that reciprocal inhibitory connections between closely spaced SBACs should be spatially selective, while connections between more widely spaced cells could be indiscriminate. SBACs were initially identified as cholinergic neurons and were subsequently shown to contain release both acetylcholine and GABA. While the role of the GABAergic transmission is well established, the role of the cholinergic transmission remains unclear.

Blocking GABAA-receptor-mediated inhibition reduces the selectivity of striate cortical neurons for the orientation of a light bar primarily by reducing the selectivity of their onset transient (initial 200 ms) response. Blocking GABAB-receptor-mediated inhibition with phaclofen, however, is not reported to reduce the orientation selectivity of these neurons when it is measured with a light bar. We hypothesized that blocking GABAB-receptor-mediated inhibition would instead affect the orientation selectivity of cortical neurons by reducing the selectivity of their sustained response to a prolonged stimulus. To test this hypothesis, we stimulated 21 striate cortical neurons with drifting sine-wave gratings and measured their orientation selectivity before, during, and after iontophoretic injection of 2-hydroxy-saclofen (2-OH-S), a selective GABAB-receptor antagonist. 2-OH-S reduced the orientation selectivity of six of eight simple cells by an average of 28.8 (± 13.2)% and reduced the orientation selectivity of eight of 13 complex cells by an average of 32.3 (± 27.4)%. As predicted, 2-OH-S reduced the orientation selectivity of the neurons' sustained response, but did not reduce the orientation selectivity of their onset transient response. 2-OH-S also increased the length of spike “bursts” (two or more spikes with interspike intervals ≤ 8 ms) and eliminated the orientation selectivity of these bursts for six cells. These results are the first demonstration of a functional role for GABAB receptors in visual cortex and support the hypothesis that two GABA-mediated inhibitory mechanisms, one fast and the other slow, operate within the striate cortex to shape the response properties of individual neurons.