Effects of Glutamate Antagonists on Goldfish Temporal Transfer Properties Measured with the Erg

s short oral presentations: EFFECTS OF GLUTAMATE ANTAGONISTS ON GOLDFISH TEMPORAL TRANSFER PROPERTIES MEASURED WITH THE ERG C.Mora-Ferrer, C.Albrecht, B.Benkner, B.Lux, M.Gruber & K.Behrend, Inst. Zoologie III, Abt. Neurobiologie, Johannes Gutenberg Univ., 55099 Mainz, Germany Purpose: Synaptic transmission from photoreceptors to bipolar cells, from bipolar cells to ganglion cells, and from bipolar cells to amacrine cells is mediated by glutamate. The different response properties, e.g. “ON” and “OFF”, are generated through different glutamate receptor (Glu-R) types on “ON”and “OFF”-bipolar cells, post-synaptic elements in the inner retina, their respective Glu-R and direct and indirect effects on bipolar cell output. Temporal transfer properties (TTP) at retinal level have been described to depend mainly upon the “OFF”-response and are characterized as a 3 order filter with resonance (Mora-Ferrer & Behrend, 2004). The contribution of the “OFF”-response to the TTP was analyzed through the use of different Glu-R antagonists. Method: Photopic ERGs were recorded from the vitreous of anesthetized and immobilized goldfish. Both background and test light illumination was provided by a LED. Stimuli used were “ON”and “OFF”-stimuli, i.e. light intensity increases and decreases of different durations, and periodic sine-wave flicker of different flicker frequencies. Drugs (calculated intraoccular concentrations in microM, APB: 100, DNQX: 50, CNQX: 10, CGS-19755: 1.5) were injected, alone or in combination, intravitreally after recording pre-injection data and then measurements were repeated. Results: Responses to “ON-OFF”-stimuli post-injection of drugs blocking AMPA/Kainate-type Glu-R (DNQX) alone exhibit a drastic reduction of the “OFF”-response best seen in the DC-part interpreted as the balance between the sustained “ON”and “OFF”-bipolar cell response. A similar result can be seen for the combination of DNQX-CNQX with CNQX also blocking the NMDA-Glu-R type. Blockade of NMDA-R alone (CGS-19755) increased the “OFF”-response amplitude. The combination of CGS 19755-DNQX resulted in a massively increased b-wave and a minute “OFF”-response to an “ON”-light stimulus. APB, a class III mGlu-R agonist, slightly lowered both the b-wave and “OFF”-response to an “ON”stimulus and increased the response to an “OFF”-stimulus. Temporal filter characteristics are not changed, as seen in the “gain”-part of the bode-plot, post-injection of APB and CGS 19755 except for the corner frequency, at the -3 db point, which moved from ~23 Hz to ~14 Hz. Post-injection of all other drugs or combinations of them, the characteristics changed to pure low-pass with varying corner frequencies between ~4 (DNQX-CNQX), 7 (DNQX) and 11 (DNQX-CGS 19755) Hz. Conclusions: DNQX changed the course of the ERG to a pure “ON”-ERG, probably by effectively eliminating the “OFF”-component to an “ON”-stimulus, changing both the corner frequency and the filter characteristics. CGS 19755 enhanced both the “ON”and “OFF”-ERG component to an “ON”stimulus which is reflected by the gain-plot. The combination of CGS 19755-DNQX resulted in a increase of the corner frequency compared to DNQX alone, probably due to the CGS-enhanced “ON”and “OFF”-component of the flash stimulus response. In contrast, CNQX-DNQX, resulted in a “ON”-flash response comparable to the one of DNQX alone, but the TTP changed even more to a pure 1 order low pass and the corner frequency shifted to ~4 Hz. In general, eliminating the “OFF”component of the ERG results in the predicted effect, i.e. the TTP is dominated by the fast processing properties in the retinal “OFF”-pathway, mostly in the inner plexiform layer. Under photopic illumination conditions APB had little to no effect on the flash response as well as on the TTP.