Perisomatic voltage-gated sodium channels actively maintain linear synaptic integration in principal neurons of the medial superior olive.
Perisomatic voltage-gated sodium channels actively maintain linear synaptic integration in principal neurons of the medial superior olive.
复制标题
DOI：
10.1523/jneurosci.2385-09.2010
复制
发表时间：
2010-02-10
期刊：
影响因子：
--
通讯作者：
Golding NL
中科院分区：
文献类型：
--
作者：
Scott LL;Mathews PJ;Golding NL
内侧上橄榄(MSO)的主神经元通过整合来自每只耳朵的锁相输入来计算方位声位置。虽然先前的实验和模型研究表明，电压门控钠通道(VGSCs)在MSO的突触整合中起着重要作用，但这些研究似乎与动作电位异常微弱的主动反向传播进入胞体和树突相矛盾。为了了解VGSCs的空间定位和生物物理特性，我们分离了沙土鼠脑干脑片中MSO主神经元的钠电流。有核和细胞贴附的斑块显示，VGSC在胞体的密度与许多其他类型的神经元相当，但在树突中大部分没有通道表达。此外，尽管体细胞VGSCs以常规电压依赖方式激活(V1/2=−30 mV)，但它们表现出异常负的稳态失活范围(V1/2=−77 mV)，使约92%的VGSCs在静息电压(~−58 mV)下失活。在电流钳实验中，未灭活的VGSC足以放大接近动作电位阈值的亚阈值EPSP，抵消了低电压激活的钾通道对EPSP峰的抑制。EPSP扩增仅限于神经元的周边区，对先前的抑制相对不敏感。最后，计算模型显示，将VGSCs排除在树突之外可以使突触部位的体细胞EPSP扩增相等，并降低了双侧与单侧兴奋性突触输入的阈值。综上所述，这些发现表明，MSO神经元的钠通道表达模式有助于这些神经元对重合的双耳输入的选择性。
Principal neurons of the medial superior olive (MSO) compute azimuthal sound location by integrating phase-locked inputs from each ear. While previous experimental and modeling studies have proposed that voltage-gated sodium channels (VGSCs) play an important role in synaptic integration in the MSO, these studies appear at odds with the unusually weak active backpropagation of action potentials into the soma and dendrites. To understand the spatial localization and biophysical properties of VGSCs, we isolated sodium currents in MSO principal neurons in gerbil brainstem slices. Nucleated and cell-attached patches revealed that VGSC density at the soma is comparable to that of many other neuron types, but channel expression is largely absent from the dendrites. Further, while somatic VGSCs activated with conventional voltage dependence (V1/2 = −30 mV), they exhibited an unusually negative range of steady-state inactivation (V1/2 = − 77 mV), leaving ~92% of VGSCs inactivated at the resting potential (~ −58 mV). In current-clamp experiments, non-inactivated VGSCs were sufficient to amplify subthreshold EPSPs near action potential threshold, counterbalancing the suppression of EPSP peaks by low voltage-activated potassium channels. EPSP amplification was restricted to the perisomatic region of the neuron, and relatively insensitive to preceding inhibition. Finally, computational modeling showed that the exclusion of VGSCs from the dendrites equalizes somatic EPSP amplification across synaptic locations and lowered the threshold for bilateral vs. unilateral excitatory synaptic inputs. Taken together, these findings suggest that the pattern of sodium channel expression in MSO neurons contributes to these neurons’ selectivity for coincident binaural inputs.