Bipolar cell morphology and GABA evoked responses in wild type and GABAC null mice

Abstract

Abstract: : Purpose: Bipolar cells (BCs) have been classified in the rat into ten groups based on their morphology and the relative proportions of GABA_A and GABA_C receptor–mediated responses to GABA application. Because a similar classification does not exist for the mouse, we characterized the morphologies and GABA responses in BCs in both WT and GABA_C null mice Methods: Current responses to GABA puffs onto the axon terminals of BCs were recorded in the whole–cell voltage clamp configuration from retinal slices in WT and GABA_C null mice. Receptor–specific GABA currents were isolated with the GABA_A and GABA_C blockers, bicuculline and TPMPA, respectively. Lucifer yellow was included in the recording pipettes to morphologically identify BCs. Results: Nine different morphological types of BCs were found in WT mice, as well as in GABA_C null mice. Rod bipolar cells (RBCs) were most frequently encountered (∼50% of BCs). Among cone bipolar cells (CBCs), we observed all of the ON and OFF types described in the rat, with the exception of OFF CB Type 1. In WT BCs, the relative proportions of GABA currents that could be attributed to either GABA_A or GABA_C varied by cell type. RBCs exhibited the largest proportion of GABA_C receptor–mediated current (∼86%), followed by ON CBCs and, OFF CBCs exhibited the smallest GABA_C–mediated currents (∼ 50%). In contrast, the RBCs and CBCs in GABA_C null mice exhibited only a GABA_Areceptor–mediated response to GABA puffs. Conclusions:In mouse retina, morphological classes of BCs were similar to those in the rat and the absence of the GABA_C receptor did not significantly alter the morphology or the proportion of any BC class. In WT mice, BC responses to GABA were a mixture of GABA_A and GABA_C receptor–mediated currents. In contrast, in GABA_C null mice BC responses to GABA application were significantly altered, and were only mediated by GABA_A receptors. These findings indicate that visual signaling, via both rod and cone pathways, should be altered in GABA_C null mice, although differential effects may be expected through the ON vs.OFF pathways.

Keywords: bipolar cells • inhibitory receptors • electrophysiology: non–clinical