Imperfect space clamp permits electrotonic interactions between inhibitory and excitatory synaptic conductances, distorting voltage clamp recordings.

Imperfect space clamp permits electrotonic interactions between inhibitory and excitatory synaptic conductances, distorting voltage clamp recordings.
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DOI:
10.1371/journal.pone.0019463
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发表时间:
2011-04-29
期刊:
影响因子:
3.7
通讯作者:
Diamond JS
Diamond JS
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Poleg-Polsky A;Diamond JS

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电压钳技术常用于检测神经元突触输入的强度和组成。即使考虑到整个细胞膜的不完美电压控制(“空间钳”),人们通常认为在索马测量的电流是突触后电导的比例指标。在这里,使用NEURON模拟软件从形态逼真的神经元模型体记录,我们表明,在电压钳模式下记录的兴奋性电导被扭曲显着相邻的抑制性电导,即使当突触后膜电位开始在抑制性电导的反转电位。当在兴奋性电导的反转电位下记录抑制性突触后电流时,观察到类似的效应。在夹闭不良的树突的逃逸电位降低的兴奋性或抑制性突触后电流的振幅记录在其他电导的逆转电位。此外,非钳位突触后抑制电导线性化记录的电流-电压关系的兴奋性输入,包括AMPAR和NMDAR介导的组件,导致显着低估的相对贡献NMDAR,这是特别敏感的膜电位的小扰动。电压钳的准确性在不同形态的神经元和树突之间变化很大;正如预期的那样,从索马附近的树突获得更可靠的记录,但是当突触后相互作用存在时,薄的、远的树突上高达80%的突触信号可能丢失。电压钳技术的这些局限性可以解释为什么在某些情况下,突触传递的突触后效应会被错误地归因于突触前机制。
The voltage clamp technique is frequently used to examine the strength and composition of synaptic input to neurons. Even accounting for imperfect voltage control of the entire cell membrane (“space clamp”), it is often assumed that currents measured at the soma are a proportional indicator of the postsynaptic conductance. Here, using NEURON simulation software to model somatic recordings from morphologically realistic neurons, we show that excitatory conductances recorded in voltage clamp mode are distorted significantly by neighboring inhibitory conductances, even when the postsynaptic membrane potential starts at the reversal potential of the inhibitory conductance. Analogous effects are observed when inhibitory postsynaptic currents are recorded at the reversal potential of the excitatory conductance. Escape potentials in poorly clamped dendrites reduce the amplitude of excitatory or inhibitory postsynaptic currents recorded at the reversal potential of the other conductance. In addition, unclamped postsynaptic inhibitory conductances linearize the recorded current-voltage relationship of excitatory inputs comprising AMPAR and NMDAR-mediated components, leading to significant underestimation of the relative contribution by NMDARs, which are particularly sensitive to small perturbations in membrane potential. Voltage clamp accuracy varies substantially between neurons and dendritic arbors of different morphology; as expected, more reliable recordings are obtained from dendrites near the soma, but up to 80% of the synaptic signal on thin, distant dendrites may be lost when postsynaptic interactions are present. These limitations of the voltage clamp technique may explain how postsynaptic effects on synaptic transmission could, in some cases, be attributed incorrectly to presynaptic mechanisms.
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