Department of Anatomy, Neuroscience Institute, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada.
J Neurosci. 2011 Mar 30;31(13):5000-12. doi: 10.1523/JNEUROSCI.5800-10.2011.
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 Ca(2+) channels (0.5 mm Cd(2+) and 0.5 mm Ni(2+)), 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 rd1 retina that is likely to drive synaptic activity in downstream circuits.
视网膜变性 (RD) 过程中光感受器的丧失已知会导致残余神经网络的基础活动增加。为了确定活动的来源，我们结合双光子成像和膜片钳技术，检查 RD 模型 (rd1) 中小鼠视网膜神经元的形态学鉴定的生理特性。对 rd1 神经节细胞活性的分析表明，在所有细胞类型中，约 30%的细胞持续表现出振荡性 (∼10 Hz) 突触活性。在药理学阻断残余光感受器、杆状双极细胞和抑制性无长突细胞突触的潜在输入后，振荡活性仍然存在，这表明前突触视锥双极细胞具有内在活性。对前突触 rd1 ON 和 OFF 双极细胞的检查表明，它们处于相对负电位 (小于 -50 mV)。然而，在大约一半的视锥双极细胞中，出现了低幅度膜振荡 (∼5 mV，∼10 Hz)。在 AII 无长突细胞中也观察到了这种振荡。ON 视锥双极细胞和 AII 无长突细胞的振荡表现出较弱的明显电压依赖性，并且对突触受体阻断剂具有抗性，这表明，与野生型视网膜一样，它们形成了一个电耦合网络。此外，振荡对电压门控 Ca(2+)通道阻断剂 (0.5 mM Cd(2+) 和 0.5 mM Ni(2+)) 不敏感，排除了在双极细胞中产生振荡行为的已知机制。综上所述，这些结果表明，ON 视锥双极/AII 无长突细胞的电耦合网络构成了 rd1 视网膜中的内在振荡器，可能会驱动下游回路中的突触活性。
