Increased Excitability and Reduced Excitatory Synaptic Input Into Fast-Spiking CA2 Interneurons After Enzymatic Attenuation of Extracellular Matrix.

Increased Excitability and Reduced Excitatory Synaptic Input Into Fast-Spiking CA2 Interneurons After Enzymatic Attenuation of Extracellular Matrix.
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DOI:
10.3389/fncel.2018.00149
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发表时间:
2018
影响因子:
5.3
通讯作者:
Dityatev A
Dityatev A
中科院分区:
医学2区
文献类型:
--
作者:
Hayani H;Song I;Dityatev A

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神经细胞外基质(ECM)富含透明质酸、硫酸软骨素蛋白聚糖(CSPG)和糖蛋白腱生蛋白-R,其在突触可塑性中起重要作用,如海马CA 1区的研究所示。然而,ECM分子在CA 2区域强烈表达,该区域包含大量的快速尖峰中间神经元(FSI),其被ECM的特别浓缩形式(神经元周网)包围。尽管有这种有趣的特性,ECM在CA 2区的功能作用大多是未知的。在这里,我们调查的急性和延迟的影响,软骨素酶ABC(ChABC),一种酶,crossts硫酸软骨素侧链的CSPGs和大大减弱神经ECM,对神经元的兴奋性和兴奋性的传输在CA 2区。用全细胞膜片钳技术记录海马脑片CA 2区锥体细胞(PC)和FSI,结果表明,ChABC注入海马CA 2区7天后,FSI和PC的兴奋性发生改变。与对照组相比,FSI产生的动作电位具有更大的振幅和更长的持续时间,以响应更少的去极化电流。在较低的去极化膜电位下,PC被激活,导致较低的锋电位产生潜伏期。FSI中兴奋性突触后电流的频率选择性降低,而抑制性突触后电流的频率选择性增加。用ChABC对海马切片进行急性处理不会导致任何这些影响。ECM衰减后FSI的兴奋性增加和突触输入变化表明与FSI相关的神经元周围网络在调节这些细胞的突触和电特性中起着至关重要的作用。
The neural extracellular matrix (ECM) is enriched with hyaluronic acid, chondroitin sulfate proteoglycans (CSPGs) and the glycoprotein tenascin-R, which play important roles in synaptic plasticity, as shown by studies of the CA1 region of the hippocampus. However, ECM molecules are strongly expressed in the CA2 region, which harbors a high number of fast-spiking interneurons (FSIs) surrounded by a particularly condensed form of ECM, perineuronal nets. Despite this intriguing peculiarity, the functional role of ECM in the CA2 region is mostly unknown. Here, we investigate the acute and delayed effects of chondroitinase ABC (ChABC), an enzyme that digests chondroitin sulfate side chains of CSPGs and greatly attenuates neural ECM, on neuronal excitability and excitatory transmission in the CA2 region. Whole-cell patch clamp recordings of CA2 pyramidal cells (PCs) and FSIs in hippocampal slices revealed that 7 days after injection of ChABC into the CA2 region in vivo, there are alterations in excitability of FSIs and PCs. FSIs generated action potentials with larger amplitudes and longer durations in response to less depolarizing currents compared to controls. PCs were excited at less depolarized membrane potentials, resulted in lower latency of spike generation. The frequency of excitatory postsynaptic currents in FSIs was selectively reduced, while the frequency of inhibitory postsynaptic currents was selectively increased. Acute treatment of hippocampal slices with ChABC did not result in any of these effects. This increase in excitability and changes in synaptic inputs to FSIs after attenuation of ECM suggests a crucial role for perineuronal nets associated with FSIs in regulation of synaptic and electrical properties of these cells.
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