Effects of Cb1–R Activation in the Goldfish Retina: Temporal Transfer Properties and Photoreceptor Intensity Response Function

Abstract

Abstract: : Purpose:CB1–receptors have been localized on numerous retinal cells. These receptors are involved in the modulation of numerous membrane conductances such as I_(h) and voltage–gated potassium channels. Interactions of cannabinoid and dopamine (DA) effects have been described both for cones and bipolar cells. DA modulates through DA–receptor temporal transfer properties of the goldfish retina and temporal resolution in behavioral experiments. To investigate whether activation of CB1–R has any effect on temporal transfer properties (TTP) for isolated photoreceptors, the intact retina or the intensity response function (IRF) of isolated photoreceptors ERG–recordings were performed in goldfish.Methods: ERGs were recorded from the vitreous body of adult goldfish under photopic illumination conditions. Background illumination and light stimuli, either square wave light ON–pulses or sinusoidal flicker (2–50 Hz), were generated with a LED. CB1–R were activated with WIN 552122–2 (WIN) in concentrations ranging between 0.03–3 µM. Isolation of photoreceptor responses was achieved with 50 mM aspartate. Results: The TTP of the intact retina was unaltered by 0.3 µM WIN (n=5), but significantly changed by 3 µM WIN (n=9), losing its' inner retina–dependent gain amplification towards the high frequency end. In contrast, the TTP of isolated photoreceptors was not changed by any WIN concentration (3, 0.3 and 0.03 µM; n= 3 per concentration) used. Also the IRF for the isolated photoreceptors was not significantly changed by 0.3 µM WIN'(n=9). Single flash responses (100 ms ON–Stimulus) of isolated photoreceptors however, increased in a dose–dependent manner by about 130 % (0.03 and 0.1 µM WIN) to about 280 % (3 µM WIN; n=3 for all concentrations). Conclusions: Although the time–course of single flash response was not affected, the TTP for the intact retina showed a loss of high frequency responsiveness. This is not based on changes in the photoreceptor responsiveness, i.e. their intensity–transfer properties or their response dynamics. The effects seen in the TTP of the intact retina must result from WIN–effects in the inner retina circuitry. Activation of CB1–R seems to affect the bipolar–amacrine–bipolar interaction which shapes the TTP of the goldfish retina.

Keywords: retina • retinal connections, networks, circuitry • temporal vision