Intrinsic bursting of AII amacrine cells underlies oscillations in the rd1 mouse retina

• Published in: Journal of neurophysiology 2014-09, Vol.112 (6), p.1491-1504
• Main Authors: Choi, Hannah, Zhang, Lei, Cembrowski, Mark S, Sabottke, Carl F, Markowitz, Alexander L, Butts, Daniel A, Kath, William L, Singer, Joshua H, Riecke, Hermann
• Format: Article
• Language: English
• Subjects: Action Potentials; Amacrine Cells - metabolism; Amacrine Cells - physiology; Animals; Cellular and Molecular Properties of Neurons; Cyclic Nucleotide Phosphodiesterases, Type 6 - genetics; Cyclic Nucleotide Phosphodiesterases, Type 6 - metabolism; Excitatory Postsynaptic Potentials; Membrane Potentials; Mice; Models, Neurological; Potassium - metabolism; Retinal Cone Photoreceptor Cells - metabolism; Retinal Cone Photoreceptor Cells - physiology; Retinal Degeneration - genetics; Retinal Degeneration - physiopathology; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - physiology; Sodium - metabolism
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00437.2014

In many forms of retinal degeneration, photoreceptors die but inner retinal circuits remain intact. In the rd1 mouse, an established model for blinding retinal diseases, spontaneous activity in the coupled network of AII amacrine and ON cone bipolar cells leads to rhythmic bursting of ganglion cells. Since such activity could impair retinal and/or cortical responses to restored photoreceptor function, understanding its nature is important for developing treatments of retinal pathologies. Here we analyzed a compartmental model of the wild-type mouse AII amacrine cell to predict that the cell's intrinsic membrane properties, specifically, interacting fast Na and slow, M-type K conductances, would allow its membrane potential to oscillate when light-evoked excitatory synaptic inputs were withdrawn following photoreceptor degeneration. We tested and confirmed this hypothesis experimentally by recording from AIIs in a slice preparation of rd1 retina. Additionally, recordings from ganglion cells in a whole mount preparation of rd1 retina demonstrated that activity in AIIs was propagated unchanged to elicit bursts of action potentials in ganglion cells. We conclude that oscillations are not an emergent property of a degenerated retinal network. Rather, they arise largely from the intrinsic properties of a single retinal interneuron, the AII amacrine cell.