Elimination Of The GABAC Receptor Alters Inner Retinal Signaling In The Cone Pathway

Abstract

Abstract: : Purpose:To determine the effects of the elimination of the GABA_C receptor on retinal processing through the cone pathways. Methods:GABA receptor mediated currents were measured in cone bipolar cells using whole cell patch clamp techniques in retinal slices from GABA_Cρ1 null mice and their wild type (WT) control littermates. Light adapted ERGs were recorded to light flashes of varying intensity and duration and to sinusoidally modulated light stimuli whose temporal frequencies varied between 4 and 48 Hz. Results:We eliminated the GABA_Cρ1 subunit in mice using gene targeting. The mice failed to express the GABA_C receptor. In WT cone bipolar cells, whole cell patch clamp demonstrated the presence of a combination of GABA_A and GABA_C mediated responses to GABA puffs at their axon terminals. In contrast, in cone bipolar cells of GABA_Cρ1 null mice the GABA response was mediated exclusively by bicuculline sensitive GABA_A receptors. Using strobe flash stimuli of varying intensities on a rod adapting background, the a- and b-waves of the ERG were similar in GABA_Cρ1 null and WT mice. In comparison, the high frequency components of the ERG, the oscillatory potentials, were increased in both amplitude and number in the GABA_Cρ1 null mice. Oscillatory potentials occurred for the entire duration of a 200 ms flash, unlike the response recorded in WT mice. Using sinusoidal stimuli to examine outer retinal function, the responses from WT and GABA_Cρ1 null mice were also similar, defining a low pass temporal response function. Conclusion:These data indicate that the GABA_Cρ1 subunit is critical to normal function of the GABA_C receptor in the cone pathway, as well as in the rod pathway in vivo. Cone photoreceptor function is not altered in the absence of the GABA_C receptor, however, components of the ERG associated with inner retinal circuitry, the oscillatory potentials, are significantly changed. The GABA_C receptor is important in the function of the cone pathway.

Keywords: 330 bipolar cells • 439 inhibitory neurotransmitters • 606 transgenics/knock-outs