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- Title
An Intrinsic Neural Oscillator in the Degenerating Mouse Retina.
- Authors
Borowska, Joanna; Trenholm, Stuart; Awatramani, Gautam B.
- Abstract
The loss of photoreceptors during retinal degeneration (RD) is known to lead to an increase in basal activity in remnant neural networks. To identify the source of activity, we combined two-photon imaging with patch-clamp techniques to examine the physiological properties of morphologically identified retinal neurons in a mouse model of RD (rd1). Analysis of activity in rd1 ganglion cells revealed sustained oscillatory (~10 Hz) synaptic activity in ~30% of all classes of cells. Oscillatory activity persisted after putative inputs from residual photoreceptor, rod bipolar cell, and inhibitory amacrine cell synapses were pharmacologically blocked, suggesting that presynaptic cone bipolar cells were intrinsically active. Examination of presynaptic rd1 ON and OFF bipolar cells indicated that they rested at relatively negative potentials (less than -50 mV). However, in approximately half the cone bipolar cells, low-amplitude membrane oscillation (~5 mV, ~10 Hz) were apparent. Such oscillations were also observed in AII amacrine cells. Oscillations in ON cone bipolar and AII amacrine cells exhibited a weak apparent voltage dependence and were resistant to blockade of synaptic receptors, suggesting that, as in wild-type retina, they form an electrically coupled network. In addition, oscillations were insensitive to blockers of voltage-gated Ca2+ channels (0.5 mM Cd2+and 0.5 mM Ni2+), ruling out known mechanisms that underlie oscillatory behavior in bipolar cells. Together, these results indicate that an electrically coupled network ofONcone bipolar/AII amacrine cells constitutes an intrinsic oscillator in the rd1 retina that is likely to drive synaptic activity in downstream circuits.
- Subjects
PHOTORECEPTORS; RETINAL degeneration; NEURAL circuitry; PATCH-clamp techniques (Electrophysiology); LABORATORY mice; ANIMAL models in research
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 13, p5000
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5800-10.2011