Abstract
Purpose: :
To examine the efficacy of local glutamate micro-application on retinal ganglion cell (RGC) response characteristics for the development of a neurotransmitter-based retinal prosthesis.
Methods: :
Flattened whole-mount retinas were prepared from Sprague-Dawley rats following enzymatic vitrectomy. RGC activity was recorded extracellularly with glass micropipettes. Responses to light and local pressure ejection of glutamate from micropipettes were examined.
Results: :
Localized glutamate application excited 70% of RGCs within 50 µm of the ejection site. RGC responses to glutamate application varied from single spikes to short duration (400 ms) activity bursts, depending on the duration (20 to 400 ms) of application. Epiretinal surface application of glutamate (2 to 10 mM) excited 51% of RGCs up to 50 µm from ejection sites whereas subsurface (50 µm below epiretinal surface) application of 2 or 5 mM glutamate excited 75% of RGCs up to 200 µm from ejection sites. The maximal response rates and durations for ON and OFF RGCs were not significantly different. The latency to response onset in OFF RGCs was 346 ± 117 ms (mean ± S.E.) and was significantly longer than that of ON RGCs (231 ± 81 ms), p=0.025. Suppression of activity was also observed (latency < 100 ms), prior to excitation, in most spontaneously active RGCs after glutamate application. This suppression may explain the long response latency of all RGCs. A secondary excitatory response was occasionally observed. Sequential glutamate applications usually evoked consistent responses, though responses were often slightly decreased even when a second application was applied up to 4 sec after prior stimulation. Two distinguishable responses to sequential applications of glutamate were observed with inter-stimulus intervals in the range of 200ms.
Keywords: ganglion cells • excitatory neurotransmitters • retina: neurochemistry