Michalikova Martina, Remme Michiel W H, Kempter Richard
Institute for Theoretical Biology, Department of Biology, Humboldt-Universität zu Berlin, Berlin , Germany.
Bernstein Center for Computational Neuroscience Berlin , Berlin , Germany.
J Neurophysiol. 2018 Oct 1;120(4):1484-1495. doi: 10.1152/jn.00463.2017. Epub 2018 Jun 27.
Spikelets are small spike-like membrane depolarizations measured at the soma whose origin in pyramidal neurons is still unresolved. We investigated the mechanism of spikelet generation using detailed models of pyramidal neurons. We simulated extracellular waveforms associated with action potentials and spikelets and compared these with experimental data obtained by Chorev and Brecht ( J Neurophysiol 108: 1584-1593, 2012) from hippocampal pyramidal neurons in vivo. We considered spikelets originating in the axon of a single cell as well as spikelets generated in two cells coupled with gap junctions. We found that in both cases the experimental data can be explained by an axonal origin of spikelets: in the single-cell case, action potentials are generated in the axon but fail to activate the soma. Such spikelets can be evoked by dendritic input. Alternatively, spikelets resulting from axoaxonal gap junction coupling with a large (greater than several hundred μm) distance between the somata of the coupled cells are also consistent with the data. Our results demonstrate that a cell firing a somatic spikelet generates a detectable extracellular potential that is different from the action potential-correlated extracellular waveform generated by the same cell and recorded at the same location. This, together with the absence of a refractory period between action potentials and spikelets, implies that spikelets and action potentials generated in one cell may easily get misclassified in extracellular recordings as two different cells, albeit they both constitute the output of a single pyramidal neuron. NEW & NOTEWORTHY We addressed the origin of spikelets, using compartmental models of pyramidal neurons. Comparing our simulation results with published extracellular spikelet recordings revealed an axonal origin of spikelets. Our results imply that action potential- and spikelet-associated extracellular waveforms may easily get misclassified as two different cells, albeit they both constitute the output of a single pyramidal cell.
小棘波是在胞体处测量到的小的、类似锋电位的膜去极化，其在锥体神经元中的起源仍未明确。我们使用锥体神经元的详细模型研究了小棘波产生的机制。我们模拟了与动作电位和小棘波相关的细胞外波形，并将其与Chorev和Brecht（《神经生理学杂志》108: 1584 - 1593, 2012）在体内海马锥体神经元中获得的实验数据进行比较。我们考虑了起源于单个细胞轴突的小棘波以及在通过缝隙连接耦合的两个细胞中产生的小棘波。我们发现，在这两种情况下，实验数据都可以用小棘波的轴突起源来解释：在单细胞情况下，动作电位在轴突中产生，但未能激活胞体。这种小棘波可由树突输入诱发。另外，由轴 - 轴突缝隙连接耦合产生的小棘波，且耦合细胞的胞体之间距离较大（大于几百微米），也与数据相符。我们的结果表明，产生体细胞小棘波的细胞会产生一种可检测到的细胞外电位，该电位不同于由同一细胞产生并在同一位置记录的与动作电位相关的细胞外波形。这一点，再加上动作电位和小棘波之间不存在不应期，意味着在一个细胞中产生的小棘波和动作电位在细胞外记录中可能很容易被错误分类为两个不同的细胞，尽管它们都是单个锥体神经元的输出。新内容与值得注意之处 我们使用锥体神经元的房室模型研究了小棘波的起源。将我们的模拟结果与已发表的细胞外小棘波记录进行比较，揭示了小棘波的轴突起源。我们的结果表明，与动作电位和小棘波相关的细胞外波形可能很容易被错误分类为两个不同的细胞，尽管它们都是单个锥体细胞的输出。
