An intrinsic neural oscillator in the degenerating XXXX retina.

@entity2000 @entity3280 @entity19 @entity3411 @entity141 @entity258 @entity734 @entity27763
The loss of photoreceptors during @entity2000 (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 @entity19 model of RD ( @entity27763 ). Analysis of activity in @entity27763 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 @entity27763 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, @entity258 (   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 @entity734 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 @entity141 channels (0.5 mm @entity3280 and 0.5 mm @entity3411 ), ruling out known mechanisms that underlie oscillatory behavior in bipolar cells. Together, these results indicate that an electrically coupled network of ON cone bipolar/AII amacrine cells constitutes an intrinsic oscillator in the @entity27763 retina that is likely to drive synaptic activity in downstream circuits.
