持续的Na+和m型K+电流相反地控制CA3锥体细胞的尖峰增益

IF 5.1 2区 医学 Q1 NEUROSCIENCES
Idit Tamir, Yoel Yaari
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引用次数: 0

摘要

神经放电反应增益和脉冲阈值是决定神经元输入输出关系的关键细胞特性。海马锥体细胞(PCs)这些细胞特性的改变可能强烈影响健康和疾病中的网络动力学。在这里,我们研究了在接近生理条件下,特定电压门控电导如何影响成年大鼠海马CA3锥体细胞(PCs)切片的这些特性。我们研究了近阈值电位激活的电流-持续钠电流(INAP), t型Ca2+电流(ICaT), m型K+电流(IM), SK Ca2+依赖电流(ISK)和h型阳离子电流(Ih)通过药理学调节和分析产生的变化。CA3 pc在放电响应增益方面表现出高度的异质性,可能反映了静止时有源电导的个体差异。用利鲁唑阻断INAP会降低放电反应增益,这一效应与诱发尖峰序列的去极化移位(DS)减少有关。相反,用XE991阻断IM可显著增加发射响应增益,降低DS,增加输入电阻,降低尖峰阈值。雷沙滨增强IM产生相反的效果。用apamin阻断ISK可适度增强放电反应增益,而阻断ICaT和Ih对放电无影响。我们的研究发现,INaP和IM是CA3 PCs尖峰反应增益和阈值的关键决定因素,这表明这些电流的调节剂可能有效地改变海马低兴奋性或高兴奋性正常和病理状态下的神经元输入输出关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Persistent Na+ and M-type K+ currents opposingly control spike gain in CA3 pyramidal cells
Neural firing response gain and spike threshold are critical intrinsic cell properties that define input-output relations in neurons. Alterations of these cellular properties in hippocampal pyramidal cells (PCs) may strongly influence network dynamics in health and disease. Here we investigated how specific voltage-gated conductance affect these properties in adult rat CA3 pyramidal cells (PCs) in hippocampal slices under near-physiological conditions. We examined currents activated at near-threshold potential – persistent sodium current (INAP), T-type Ca2+ current (ICaT), M-type K+ current (IM), SK Ca2+ − dependent current (ISK), and h-type cationic current (Ih) through pharmacological modulation and analysis of resulting changes. CA3 PCs showed high heterogeneity in firing response gain, likely reflecting individual variations in active conductance at rest. Blocking INAP by riluzole decreased firing response gain, an effect associated with a reduction in the depolarizing shift (DS) underlying evoked spike trains. Conversely, blocking IM with XE991 markedly increased firing response gain, decreased the DS, increased input resistance, and lowered spike threshold. Enhancing IM by retigabine produced opposite effects. Blocking ISK with apamin moderately augmented firing response gain, while blocking ICaT and Ih exerted no effect on discharge.
Our findings identify INaP and IM as key determinants of spike response gain and threshold of CA3 PCs, suggesting that modulators of these currents may effectively modify neuronal input-output relations in both normal and pathological states of hippocampal hypo- or hyperexcitability.
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来源期刊
Neurobiology of Disease
Neurobiology of Disease 医学-神经科学
CiteScore
11.20
自引率
3.30%
发文量
270
审稿时长
76 days
期刊介绍: Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.
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