GABAC Receptor-mediated Inhibition Shapes Retinal Ganglion Cell Visual Responses

Abstract

Abstract: : Purpose: To assess the role of GABA_C receptor-mediated inhibition in shaping visual response properties of retinal ganglion cells (RGCs). Methods: Light-adapted (background illumination 25 cd/m²) extracellular responses were recorded in vivo from single optic nerve fibers in GABA_Cρ1 null (Null) and wild type (WT) mice. Spatially (0.01-.58 c/d) and temporally (0.1–32 Hz) modulated sine-wave gratings (drifting and contrast reversing) were used, over a range of contrasts (0–100%), to determine the receptive field properties of each cell. Spots of varying diameters (1–45 deg) also were used to assess surround antagonism and the sustained/transient nature of the response. Results: RGCs in Null (n=100) and WT (n=100) mice have receptive fields centers that are roughly circular and can be classified as either ON- or OFF-center. In WT mice, approximately equal percentages of ON- and OFF-center cells (54% and 46%) were recorded. In Null mice there were more ON center cells (80% ON vs 20% OFF), which is significantly different from WT. Several properties of Null ON-center cells differ compared to WT cells. They include: higher spontaneous activity levels and peak response amplitudes, and more sustained center responses. Although optimal temporal frequencies were similar, high frequency cutoffs, which ranged between 4.0 and 24.0 Hz, were significantly higher in Null mice compared to WT. Many response properties of cells in the two groups of mice were similar. For example, when we grouped cells according to a standard battery of tests into X-like and Y-like, we found no difference in the percentages of cells in each class across the two groups of mice. In addition, there were no differences between Null and WT cells in their optimal or high spatial frequency cutoffs for either drifting or contrast reversal gratings. No differences were noted in the response modulation of cells when the contrast of the grating stimuli was varied, nor were there differences in optimal spot diameters, determined from area response functions. Conclusion: These results begin to define the role of GABA_C receptor-mediated inhibition in shaping the visual response of RGCs. Specifically, this inhibition limits the excitatory drive in the ON pathway and may alter the balance between the ON-center cell’s receptive field center and antagonistic surround.

Keywords: ganglion cells • receptive fields • electrophysiology: non-clinical