Effects of the destruction of starburst-cholinergic amacrine cells by the toxin AF64A on rabbit retinal directional selectivity

Abstract

The effects of intraocular injections of ethylcholine mustard aziridinium ion (AF64A), an irreversible inhibitor of choline uptake, on the rabbit retina were assessed electrophysiologically, pharmacologically, anatomically, and behaviorally. Survival times from 1 day to 30 days were investigated. After 24 h, the shortest time tested, the directional selectivity of On-Off responding ganglion cells having the characteristic morphology of On-Off directionally selective directionally selective (DS) ganglion cells, as revealed by intracellular dye injection, was significantly reduced, both by an apparent decrease of preferred direction responses and an increase in responses to null-direction movement. No toxin-mediated changes in the dendritic trees of these cells were noted. Cells in AF64A-affected retinas having the DS morphology did not respond significantly to GABAergic or cholinergic agents such as picrotoxin and eserine, but did respond to nicotine. Recordings from a small random sample of other ganglion cell classes in the same retinas yielded no obvious changes in response properties. The direct effects on starburst (cholinergic) amacrine cells, which were identified by intraocular injection of the fluorescent dye DAPI with the AF64A, were investigated by intracellular injections of Lucifer yellow, and by immunohistochemical staining with antibodies to choline acetyltransferase (ChAT). Although starburst amacrine cell somas survived the AF64A treatment for at least several days, the dendrites could not be visualized by fluorescent dye injection in affected retinas due to dye leakage of the injected fluorescent dye from either the soma or proximal dendritic region. ChAT staining revealed a sequence in which ChAT-positive cells were undetectable first in the inner nuclear layer, and then in the ganglion cell layer. Cholinergic amacrine cells in the central retina were also affected before those in the periphery. The electrophysiological changes observed typically preceded the loss of ChAT activity. Behavioral tests for optokinetic nystagmus responses also revealed a lack of such responses in the affected eyes.

A Unique Role for Kv3 Voltage-Gated Potassium Channels in Starburst Amacrine Cell Signaling in Mouse Retina

“…Specific elimination of starburst cells, either through pharmacological manipulation or genetic targeting, abolishes the selectivity of DS cells (Yoshida et al, 2001;Amthor et al, 2002; but see He and Masland, 1997). Based on dual patch recordings, Fried et al (2002) showed that starburst cells provide direct inhibition to DS cells.…”

Computation of motion direction in the vertebrate retina

“…The first direct evidence for this hypothesis came from nifty studies demonstrating that selective ablation of SACs using genetic or pharmacological tools renders the responses of ON and ON-OFF DS ganglion cells indiscriminate to motion direction [1,92]. These results also suggest that SACs are a major source of DS-relevant GABAergic inhibition.…”

“…Since ablation of SACs results in a complete loss of the optokinetic nystagmus (OKN) [1,92], classic ON and ON-OFF DS cells are clearly involved. Instead of projecting to the superior colliculus (SC) and lateral geniculate nucleus (LGN) like the majority of ganglion cells, ON DS cells indeed project to the accessory optic system (AOS), a collection of nuclei that controls eye movement (for review, see [8]).…”

“…3d), which would explain why this excitatory DS pathway is also sensitive to GABA receptor blockers. The fact that ablating SACs abolishes DS responses in classic DS ganglion cells [1,92] …”

Neuropeptides, Trophic Factors, and Other Substances Providing Morphofunctional and Metabolic Protection in Experimental Models of Diabetic Retinopathy

“…These deficits could be explained by the degeneration in synaptic neurotransmission and/or combined loss of amacrine neurons and RGCs (Kern and Barber, 2008). The function of RGCs is compromised when there is a loss of dopaminergic or cholinergic signaling in the retina (Amthor et al, 2002). Loss of dopaminergic and cholinergic neurons may cause changes to visual processing that play a role in the vision loss associated with diabetes (Gastinger et al, 2006).…”