Pharmacological analysis of directionally sensitive rabbit retinal ganglion cells

Abstract

Cholinergic drugs were infused into the retinal circulation of the rabbit while the receptive field properties of directionally sensitive retinal ganglion cells were analyzed. Physostigmine eliminated the trigger feature, directional specificity, of both types (on-center and on-off) of these cells. In this respect the action of physostigmine (an ACh [acetylcholine] potentiator) was very like that of picrotoxin (a GABA antagonist). A detailed analysis of the receptive field properties of directionally sensitive ganglion cells was made to analyze the effects of physostigmine and picrotoxin. Size specificity and radial grating inhibition were not abolished by physostigmine but were often affected by picrotoxin. The optimal velocity in the preferred direction (as measured by maximum firing frequency) was not much changed by physostigmine but was higher during infusion of picrotoxin. Infusion of nicotine, a depolarizing ACh agonist which increases the activity of retinal ganglion cells, revealed the presence of inhibition to movement in the null direction. The null direction response during picrotoxin started slightly later than this inhibition. The null direction response during physostigmine was weaker and started later still. Mecamylamine and dihydro-.beta.-erythroidine, nicotinic receptor antagonists, totally blocked the effect of physostigmine and reduced the control light response by about half. From this analysis, it appears that on-off ACh release onto directionally sensitive cells provides a substantial excitation which, when potentiated by physostigmine, overcomes or outlasts the null direction GABA inhibition within the receptive field. The spatial extent of GABA inhibition is asymmetric to, and larger than, the spatial extent of ACh excitation. Similar pathways appear to be involved in both the on-center and on-off directionally sensitive ganglion cells, yet the on-center cell pathway may receive an additional input which suppresses the ACh excitation at light offset. Possible schemes for the cellular mechanism of directional sensitivity are discussed in light of these results and recent anatomical and pharmacological findings.