Intermittent Failure of Spike Propagation in Primary Afferent Neurons during Tactile Stimulation
Intermittent Failure of Spike Propagation in Primary Afferent Neurons during Tactile Stimulation
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DOI：
10.1523/jneurosci.0975-19.2019
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发表时间：
2019-12-11
影响因子：
5.3
通讯作者：
Prescott, Steven A.
中科院分区：
文献类型：
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作者：
Al-Basha, Dhekra;Prescott, Steven A.
初级传入神经元向中枢神经系统传递体感信息。低阈值机械感受器根据其在持续触觉刺激过程中是否重复放电而被分为慢适应(SA)或快适应(RA)；前者又根据其放电的规律性被细分为类型1或类型2。从小鼠的DRG中记录在体，我们观察到与SA1和SA2低阈值机械感受器一致的不规则和规则的尖峰单位，但一些我们标记为“半规则”的单位并不完全符合现有的分类方案。对它们的穗的分析揭示了整数倍模式，其中穗序列由基本的穗间间隔及其倍数组成。整数-多重模式的尖峰是通过随机地从其他规则的尖峰序列中移除尖峰来复制的，这表明半规则单元代表其中一些尖峰缺失的SA2单元。我们假设，缺失的尖峰是由于尖峰的启动或传播的间歇性失败造成的。一些观察结果排除了间歇性棘波启动失败的可能性：皮内利多卡因不能诱导整体性多模式棘波，不依赖于刺激形式(机械刺激和光遗传刺激)，不能在基于电导的模型神经元中复制给定的恒定输入。另一方面，在背根神经节上应用利多卡因可诱导出整倍型的穗电活动，从而为整倍型穗电活动的发生奠定了基础。事实上，所有SA2单位中有一半出现了一些缺失的尖峰，大多是以低速率(
Primary afferent neurons convey somatosensory information to the CNS. Low-threshold mechanoreceptors are classified as slow-adapting (SA) or rapid-adapting (RA) based on whether or not they spike repetitively during sustained tactile stimulation; the former are subclassified as Type 1 or 2 based on the regularity of their spiking. Recording in vivo from DRGs of mice, we observed irregular- and regular-spiking units consistent with SA1 and SA2 low-threshold mechanoreceptors, but some units, which we labeled "semiregular," did not fit cleanly into the existing classification scheme. Analysis of their spiking revealed integer-multiple patterning in which spike trains comprised a fundamental interspike interval and multiples thereof. Integer-multiple-patterned spiking was reproduced by randomly removing spikes from an otherwise regular spike train, suggesting that semiregular units represent SA2 units in which some spikes are "missing." We hypothesized that missing spikes arose from intermittent failure of spikes to initiate or to propagate. Intermittent failure of spike initiation was ruled out by several observations: integer-multiple-patterned spiking was not induced by intradermal lidocaine, was independent of stimulus modality (mechanical vs optogenetic), and could not be reproduced in a conductance-based model neuron given constant input. On the other hand, integer-multiple-patterned spiking was induced by application of lidocaine to the DRG, thus pinpointing intermittent failure of spike propagation as the basis for integer-multiple-patterned spiking. Indeed, half of all SA2 units exhibited some missing spikes, mostly at low rate (