The whole-cell voltage clamp technique is commonly used to estimate synaptic conductances. While previous work has shown how these estimates are affected by series resistance and space clamp errors during isolated synaptic events, how voltage clamp errors impact on synaptic conductance estimates during concurrent excitation and inhibition is less clear. This issue is particularly relevant given that many studies now use the whole-cell voltage clamp technique to estimate synaptic conductances in vivo, where both excitation and inhibition are intact. Using both simplistic and morphologically realistic models, we investigate how imperfect voltage clamp conditions distort estimates of excitatory and inhibitory synaptic conductance during concurrent synaptic input onto dendrites. These simulations demonstrate that dendritically located conductances are underestimated even when dynamic clamp reinjection faithfully reproduces the voltage response at the soma to the actual conductances. Inhibitory conductances are underestimated more than excitatory conductances, leading to errors in the excitatory to inhibitory conductance ratio and negative inhibitory conductance estimates during distal inhibition. Interactions between unclamped dendritic excitatory and inhibitory conductances also introduce correlations when the actual conductances are uncorrelated, as well as distortions in the time course of estimated excitatory and inhibitory conductances. Finally, we show that space clamp errors are exacerbated by the inclusion of dendritic voltage-activated conductances. In summary, we highlight issues with the interpretation of synaptic conductance estimates obtained using somatic whole-cell voltage clamp during concurrent excitatory and inhibitory input to neurons with dendrites.

全细胞电压钳技术通常用于估计突触电导。虽然以前的工作已经表明这些估计如何在孤立的突触事件期间受到串联电阻和空间钳位误差的影响，但电压钳位误差如何影响同时激发和抑制期间的突触电导估计尚不清楚。鉴于许多研究现在使用全细胞电压钳技术来估计体内突触电导，这个问题尤其重要，其中兴奋和抑制都是完整的。使用简单化和形态上现实的模型，我们研究了在同时输入到树突上的突触输入过程中，不完美的电压钳条件如何扭曲兴奋性和抑制性突触电导的估计。这些模拟表明，即使动态钳位再注入忠实地再现了体细胞对实际电导的电压响应，树突状电导也被低估了。抑制性电导比兴奋性电导被低估，导致兴奋性与抑制性电导比的误差和远端抑制期间的负抑制性电导估计。当实际电导不相关时，未夹紧的树突兴奋性和抑制性电导之间的相互作用也会引入相关性，以及估计的兴奋性和抑制性电导的时间过程中的扭曲。最后，我们表明，包含树枝状电压激活电导会加剧空间钳位误差。总之，我们强调了在对具有树突的神经元同时进行兴奋性和抑制性输入期间使用体细胞全细胞电压钳获得的突触电导估计值的解释问题。