A Novel Retinal Oscillation Mechanism in an Autosomal Dominant Photoreceptor Degeneration Mouse Model

• Published in: Frontiers in cellular neuroscience Vol. 9; p. 513
• Main Authors: Tu, Hung-Ya, Chen, Yu-Jiun, McQuiston, Adam R, Chiao, Chuan-Chin, Chen, Ching-Kang
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 12.01.2016; Frontiers Media S.A
• Subjects: AII amacrine cells; Amacrine cells; Animal models; Connexin 36; Dopamine receptors; Excitatory postsynaptic potentials; Gap junctions; Hyperactivity; Inhibitory postsynaptic potentials; Laboratory animals; Medicine; Neuroscience; Neurosciences; oscillation mechanism; Oscillations; photoreceptor degeneration; Photoreceptors; Retina; Retinal degeneration; Retinal ganglion cells; Rhodopsin; Rhythm; Rhythms; Rods; Starburst amacrine cell; United States > US; Taiwan; AII amacrine cells; photoreceptor degeneration; oscillation mechanism; retina; starburst amacrine cell
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2015.00513

It has been shown in rd1 and rd10 models of photoreceptor degeneration (PD) that inner retinal neurons display spontaneous and rhythmic activities. Furthermore, the rhythmic activity has been shown to require the gap junction protein connexin 36, which is likely located in AII amacrine cells (AII-ACs). In the present study, an autosomal dominant PD model called rhoΔCTA, whose rods overexpress a C-terminally truncated mutant rhodopsin and degenerate with a rate similar to that of rd1, was used to investigate the generality and mechanisms of heightened inner retinal activity following PD. To fluorescently identify cholinergic starburst amacrine cells (SACs), the rhoΔCTA mouse was introduced into a combined ChAT-IRES-Cre and Ai9 background. In this mouse, we observed excitatory postsynaptic current (EPSC) oscillation and non-rhythmic inhibitory postsynaptic current (IPSC) in both ON- and OFF-SACs. The IPSCs were more noticeable in OFF- than in ON-SACs. Similar to reported retinal ganglion cell (RGC) oscillation in rd1 mice, EPSC oscillation was synaptically driven by glutamate and sensitive to blockade of NaV channels and gap junctions. These data suggest that akin to rd1 mice, AII-AC is a prominent oscillator in rhoΔCTA mice. Surprisingly, OFF-SAC but not ON-SAC EPSC oscillation could readily be enhanced by GABAergic blockade. More importantly, weakening the AII-AC gap junction network by activating retinal dopamine receptors abolished oscillations in ON-SACs but not in OFF-SACs. Furthermore, the latter persisted in the presence of flupirtine, an M-type potassium channel activator recently reported to dampen intrinsic AII-AC bursting. These data suggest the existence of a novel oscillation mechanism in mice with PD.