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细胞外电场对丘脑网状神经元低阈电流调节树突 Ca 反应的状态依赖性调制。

State-dependent modulation of low-threshold-current-regulated dendritic Ca response in thalamic reticular neurons with extracellular electric fields.

机构信息

Tianjin Key Laboratory of Process Measurement and Control, School of Electrical and Information Engineering, Tianjin University, Tianjin, China.

School of Information Technology Engineering, Tianjin University of Technology and Education, Tianjin, 300222, China.

出版信息

Sci Rep. 2023 Oct 1;13(1):16485. doi: 10.1038/s41598-023-43611-y.

DOI:10.1038/s41598-023-43611-y
PMID:37779115
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10543533/
Abstract

Deep brain stimulation (DBS) in thalamic reticular nucleus (TRN) neuron provides a novel treatment for drug-resistant epilepsy via the induced electrical field (EFs). However, the mechanisms underlying EF effects remain unclear. This paper investigated how EFs regulate low-threshold dendritic Ca (dCa) response and thus contribute to the input-output relationship of TRN cell. Our results showed that EFs modulate firing modes differently in a neuronal state-dependent manner. At the depolarized state, EFs only regulate the spike timing of a somatic stimulus-evoked single action potential (AP) with less contribution in the regulation of dCa response but could induce the transition between a dendritic stimulus-evoked single AP and a tonic burst of APs via the moderate regulation of dCa response. At the hyperpolarized state, EFs have significant effects on the dCa response, which modulate the large dCa response-dependent burst discharge and even cause a transition from this type of burst discharge to a single AP with less dCa response. Moreover, EF effects on stimulation threshold of somatic spiking prominently depend on EF-regulated dCa responses and the onset time differences between the stimulus and EF give rise to the distinct effect in the EF regulation of dCa responses. Finally, the larger neuronal axial resistance tends to result in the dendritic stimulus-evoked dCa response independent of somatic state. Interestingly, in this case, the EF application could reproduce the similar somatic state-dependent dCa response to dendritic stimulus which occurs in the case of lower axial resistance. These results suggest that the influence of EF on neuronal activities depends on neuronal intrinsic properties, which provides insight into understanding how DBS in TRN neuron modulates epilepsy from the point of view of biophysics.

摘要

丘脑网状核(TRN)神经元的深部脑刺激(DBS)通过诱导电场(EFs)为耐药性癫痫提供了一种新的治疗方法。然而,EF 效应的机制尚不清楚。本文研究了 EFs 如何调节低阈值树突 Ca(dCa)反应,从而有助于 TRN 细胞的输入-输出关系。我们的结果表明,EFs 以神经元状态依赖的方式不同地调节放电模式。在去极化状态下,EFs 仅调节体刺激诱发的单个动作电位(AP)的尖峰时间,对 dCa 反应的调节作用较小,但通过适度调节 dCa 反应,可诱导树突刺激诱发的单个 AP 与 AP 的强直爆发之间的转变。在超极化状态下,EFs 对 dCa 反应有显著影响,调节大的 dCa 反应依赖性爆发放电,甚至导致从这种类型的爆发放电到具有较小 dCa 反应的单个 AP 的转变。此外,EF 对体峰放电刺激阈值的影响显著依赖于 EF 调节的 dCa 反应,并且刺激和 EF 之间的起始时间差异导致 EF 对 dCa 反应的调节作用明显不同。最后,较大的神经元轴向电阻往往导致与体状态无关的树突刺激诱发的 dCa 反应。有趣的是,在这种情况下,EF 应用可以再现与较低轴向电阻情况下发生的类似的树突刺激依赖性 dCa 反应。这些结果表明,EF 对神经元活动的影响取决于神经元的内在特性,这为从生物物理的角度理解 TRN 神经元的 DBS 如何调节癫痫提供了深入的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/616c035abe5a/41598_2023_43611_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/cf69711f4b19/41598_2023_43611_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/12e6fd75c634/41598_2023_43611_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/65a0e9b63d63/41598_2023_43611_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/6f6c26d6d4fc/41598_2023_43611_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/6028affaac8b/41598_2023_43611_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/616c035abe5a/41598_2023_43611_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/cf69711f4b19/41598_2023_43611_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/12e6fd75c634/41598_2023_43611_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/65a0e9b63d63/41598_2023_43611_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/6f6c26d6d4fc/41598_2023_43611_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/6028affaac8b/41598_2023_43611_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4be/10543533/616c035abe5a/41598_2023_43611_Fig6_HTML.jpg

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