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Gautam B. Awatramani, Joanna Borowska, Stuart Trenholm; Emergent Pacemaker Activity In The AII Amacrine/cone Bipolar Cell Network In The RD1 Mouse Model For Retinal Degeneration Relies On Voltage-dependent Na Currents. Invest. Ophthalmol. Vis. Sci. 2011;52(14):710.
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The loss of photoreceptors during retinal degeneration (RD) leads to intrinsic oscillatory activity in electrically coupled AII amacrine and cone bipolar cells, which triggers activity throughout the remnant retinal circuitry (Borowska et al., 2010). Spontaneous rhythmic activity likely hinders any efforts that aim to stimulate remnant circuits for purposes of vision restoration, prompting an investigation into the biophysical mechanisms that underlie such activity. Thus, we investigated the role of regenerative Na current in generating intrinsic oscillations within the electrically-coupled network of AII amacrine/bipolar cells in the rd1 mouse model for RD.
We applied patch-clamp and 2-photon imaging techniques to examine the physiological properties of identified AII amacrine and bipolar cell types in the retina of the rd1 mouse (at a stage where most of their photoreceptors have degenerated; P30-50).
AII amacrine cells and ON cone bipolar cells in the rd1, but not wt retina, exhibit a characteristic membrane oscillation (~10 Hz). These oscillations were found to be insensitive to blockers of synaptic receptors (Picrotoxin, Strychnine, NBQX and AP4, AP5) and voltage-gated Ca channels (0.5 mM Cd2+and 0.5 mM Ni2+). In contrast, bath application of 500 nM TTX, completely abolished oscillations in both AII and cone bipolar cells. Voltage-clamp recordings demonstrated the presence of inward, voltage-dependent TTX-sensitive currents in AII amacrine cells but not cone bipolar cells, suggesting that oscillations are generated in the AII amacrine cells. In addition, pharmacologically disrupting electrical connections using 0.2 mM MFA strongly inhibited oscillations in bipolar cells and AII amacrine cells. Thus, oscillatory activity appears to me an emergent property of the network rather than a property of individual AII amacrine or bipolar cells.
Na current in AII amacrine cells play an essential role in generating spontaneous oscillations. Such oscillations propagate through the remnant circuits of the rd1 retina via a combination of electrical and chemical synapses.
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