Optical current source density analysis in hippocampal organotypic culture shows that spreading depression occurs with uniquely reversing currents
Optical current source density analysis in hippocampal organotypic culture shows that spreading depression occurs with uniquely reversing currents
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DOI：
10.1523/jneurosci.0491-05.2005
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发表时间：
2005-04-13
影响因子：
5.3
通讯作者：
Kraig, RP
中科院分区：
文献类型：
--
作者：
Kunkler, PE;Hulse, RE;Kraig, RP
扩散性抑制（SD）涉及流经主要神经元的电流，但流经易感组织或单个主要神经元的电流模式仍不确定。因此，通过光电流源密度分析对经历 SD 的海马器官型培养物中电压敏感染料变化的数字成像制成的组织和单细胞图谱进行处理，以揭示与锥体神经元相关的电流。观察到两种独特的电流流动模式。第一个是随着 CA3 锥体神经元 SD 的开始而发展的三层模式 (420 μ m(2))，其中 SD 最常开始。该初始模式包括一个体细胞电流吸收器，其电流源位于树突的两侧，持续数秒，延伸到 SD 的经典“倒鞍”间质直流波形的第一个方面。接下来，体细胞汇以每分钟毫米的速度反向传播到近端树突中，导致初始电流流动模式反转至其第二方向，即与体细胞源相关的树突汇。后者在 CA3 中持续存在 SD 的其余部分，并且是 CA1 中看到的唯一模式，其中 SD 很少启动。这种反向传播的 SD 电流类似于活动依赖性突触激活。通过主神经元电流的逆行和关联信号传导是影响组织功能的关键手段，包括突触激活，甚至可能是 SD。这种与电流相关的突触后信号传导不仅有助于解释 SD，还有助于解释神经保护和偏头痛，这两种现象越来越多地被认为与 SD 相关。
Spreading depression (SD) involves current flow through principal neurons, but the pattern of current flow over the expanse of susceptible tissues or individual principal neurons remains undefined. Accordingly, tissue and single cell maps made from digital imaging of voltage-sensitive dye changes in hippocampal organotypic cultures undergoing SD were processed via optical current source density analysis to reveal the currents associated with pyramidal neurons. Two distinctive current flow patterns were seen. The first was a trilaminar pattern (420 mu m(2)) that developed with the onset of SD in CA3 pyramidal neurons, in which SD most often began. This initial pattern comprised a somatic current sink with current sources to either side in the dendrites that lasted for seconds extending into the first aspect of the classical "inverted saddle" interstitial direct current waveform of SD. Next, the somatic sink backpropagated at a speed of millimeters per minute into the proximal dendrites, resulting in a reversal of the initial current flow pattern to its second orientation, namely dendritic sinks associated with a somatic source. The latter persisted for the remainder of SD in CA3 and was the only pattern seen in CA1, in which SD was rarely initiated. This backpropagating SD current flow resembles that of activity-dependent synaptic activation. Retrograde and associative signaling via principal neuron current flow is a key means to affect tissue function, including synaptic activation and, by extension, perhaps SD. Such current-related postsynaptic signaling might not only help explain SD but also neuroprotection and migraine, two phenomena increasingly recognized as being related to SD.