MICROSTRUCTURE OF ELECTRICAL ACTIVITY IN CORTICAL CELLS

是什么机制导致大脑皮层神经元激发动作电位？我们 已经表明，活体中的皮质细胞不太可能 由于尖峰的时间和随机性很小 兴奋性突触输入。他们高度的射击不规则性可能会导致 来自非常强烈和快速的去极化事件(例如树枝状尖峰) 或在“整合”期间极强的再极化电流(例如 作为电压门控钾电流或亚毫微秒膜衰变时间 常量)或来自大规模抑制。我们已经在预赛中展示了 研究表明，脑片中的锥体细胞非常有规律地发射，而且 尖峰产生机制本身并不是高的来源 可变性。 我们希望研究在生理条件下突触输入是如何 触发尖峰以及这一过程如何影响非线性和 单个神经元信息的时间尺度(亚毫秒与数十毫秒) 计算。我们建议将不同的数值/分析研究 在实验室提供给我们的单细胞录音上进行 R·道格拉斯和K·马丁，以及隔室建模模拟 同时复制所有具有特征的外部和内部- 记录的细胞的细胞反应。 其中一项研究将检测亚阈值细胞内的波动 电压，通过傅立叶功率谱分析测量。另一项研究 将量化细胞触发机制的各个方面--例如在 超极化和放电“阈值”--这可能为我们提供对 这些导体的位置、时间尺度和强度。其他 研究将检验大规模抑制和慢速抑制的作用 电导，并使用算法复杂性和相关度量来 描述细胞的放电行为。我们还将研究如何 在存在不可靠突触的情况下，突触输入可导致皮质 行为猴的细胞以可靠的速度调节它们的放电率 2-10毫秒级别。所有这些分析都将与模拟进行比较 锥体细胞和星状细胞(从猫纹皮质重建) 具有被动和主动树枝状电导，并且在 相关的突触输入。其目的是找到能够 同时复制所有细胞的反应(包括它们的 可变性和它们在时间上精确调节的能力)，以及 可以简化为概念上更简单，计算要求更低 表格。我们希望这种细胞内记录的独特组合 而理论专业知识可以说明时间尺度和复杂性 单个大脑皮层细胞处理其输入的过程。

What mechanisms cause a cortical neuron to fire an action potential? We have shown previously that it is unlikely that cortical cells in vivo spike as a result of the temporal summation of small and random excitatory synaptic inputs. Their high firing irregularity could result from very strong and fast depolarizing events (such as dendritic spikes) or from extremely strong repolarizing currents during "integration" (such as voltage-gated potassium currents or sub-ms membrane decay time constants) or from massive inhibition. We have shown in preliminary studies that pyramidal cells in slice fire very regularly, and that the spike-generating mechanism itself is not the source of the high variability. We wish to study how synaptic inputs under physiological conditions trigger spikes and how this process affects both the nonlinearity and the time-scale (sub-ms vs. tens of ms) of single neuron information computation. We propose different numerical/analytical studies to be performed on single-cell recordings supplied to us from the laboratory of R. Douglas and K. Martin, and compartmental-modeling simulations to reproduce simultaneously all of the characteristic extra- and intra- cellular responses of the recorded cells. One study will examine the fluctuations in the subthreshold intracellular voltage, as measured by Fourier power-spectrum analysis. Another study will quantify aspects of the cell's firing mechanism-such as after hyperpolarization and firing "threshold"-that may provide insight into the locations, time-scales, and strengths of the conductances. Other studies will examine the contribution of massive inhibition and slower conductances, and use algorithmic complexity and related measures to characterize the cell's firing behavior. We will also examine how synaptic input in the presence of unreliable synapses can cause cortical cells in the behaving monkey to modulate their firing rate reliably at the 2-10 ms level. All of these analyses will be compared to simulations of pyramidal and stellate cells (reconstructed from cat striate cortex) with passive and active dendritic conductance and in the presence of correlated synaptic input. The aim is to find models which can simultaneously reproduce all the cells' responses (including their variability and their ability to modulate precisely in time), and which can be reduced to conceptually simpler and less computationally demanding forms. We hope that this unique combination of intracellular recordings and theoretical expertise can Illuminate the time-scale and complexity of the process by which single cortical cells process their input.