Purpose. We examined the role of GABA in modulating the spontaneous bursting activity of retinal neurons during development. Methods. Spontaneous activity of cells in the retinal ganglion cell layer (GCL) of neonatal ferrets (postnatal days, P1 to P30) was monitored using optical recording techniques and the Ca2+ indicator dye, fura-2. Whole-cell recordings were performed on cells in the GCL in retinal slices. Pharmacological agents were either superfused into the recording chamber or puffed into the inner plexiform layer next to the recorded cells. Results. During the first postnatal week, bicuculline (30-100 μM) either abolished or reduced the spontaneous activity of cells in the GCL. Between P15 and P17, bicuculline was less effective in blocking the bursting activity. By P21, bicuculline caused an increase in the bursting activity of many cells of the GCL, but the bursts of neighboring cells remained synchronized. At all ages, picrotoxin (100 μM) mimicked the effects of bicuculline. At P14, addition of the GABA uptake inhibitor, nipecotic acid (300 μM), caused either an increase in bursting or a sustained increase in [Ca2+]i. Under whole-cell voltage-clamp, GABA evoked currents in GCL neurons (P10-P28), which were abolished by bicuculline (100 μM) and by picrotoxin (100 μM). Conclusions. Early in development, GABA appears to promote the bursting behaviour of GCL neurons. However, as the retina matures, GABA reduces the bursting ability of retinal cells. GABA responses in the GCL are mediated primarily by GABAa receptors because they are antagonized by bicuculline and picrotoxin. Taken together with the results of using GABA uptake inhibitors, these findings suggest that endogenous GABA is released, presumably from amacrine cells, during the bursting activity. Although GABA can modulate the frequency of bursting, it does not appear to play a role in synchronizins the bursts of neighboring retinal cells.
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Feb 15 1996|