Synapse-Associated Protein 97 Regulates the Membrane Properties of Fast-Spiking Parvalbumin Interneurons in the Visual Cortex
Synapse-Associated Protein 97 Regulates the Membrane Properties of Fast-Spiking Parvalbumin Interneurons in the Visual Cortex
复制标题
DOI：
10.1523/jneurosci.0040-13.2013
复制
发表时间：
2013-07-31
影响因子：
5.3
通讯作者：
Wollmuth, Lonnie P.
中科院分区：
文献类型：
--
作者：
Akgul, Gulcan;Wollmuth, Lonnie P.
视皮层第2/3层中的快速尖峰小白蛋白（PV）阳性中间神经元调节视觉处理的增益控制和调谐。突触相关蛋白97（SAP 97）属于在神经系统中参与调节锥体-锥体连接处的突触能突触传递的蛋白质家族。对于小鼠视觉皮层中的PV中间神经元，SAP 97的表达是发育调节的，在几乎所有的青少年中表达，但只有一小部分，类似于40%的成年PV中间神经元。采用全细胞膜片钳技术和单细胞RT-PCR技术检测SAP 97的内源性和外源性表达，探讨SAP 97在视皮层2/3层PV中间神经元中的功能意义。PV interneurons表达SAP 97，无论是内源性或通过外源性表达，表现出不同的膜特性，从那些不表达SAP 97。这包括膜兴奋性的总体降低，如通过膜电阻降低和第一动作电位放电的刺激阈值增加所指示的。此外，SAP 97表达PV中间神经元更频繁地发射动作电位，在中等刺激强度下，表现出不规则或口吃的放电模式。此外，SAP 97表达PV中间神经元表现出增加的神经元能输入和更广泛的树突分支相比，非表达PV中间神经元。膜和突触性质的这些差异将显著改变表达SAP 97的PV中间神经元与不表达SAP 97的PV中间神经元相比在局部网络中的功能。因此，我们的研究结果表明，支架蛋白SAP 97是调节皮质PV中间神经元输入-输出关系的关键分子因子。
Fast-spiking parvalbumin (PV)-positive interneurons in layers 2/3 of the visual cortex regulate gain control and tuning of visual processing. Synapse-associated protein 97 (SAP97) belongs to a family of proteins that have been implicated in regulating glutamatergic synaptic transmission at pyramidal-to-pyramidal connections in the nervous system. For PV interneurons in mouse visual cortex, the expression of SAP97 is developmentally regulated, being expressed in almost all juvenile but only a fraction, similar to 40%, of adult PV interneurons. Using whole-cell patch-clamping, single-cell RT-PCR to assay endogenous expression of SAP97 and exogenous expression of SAP97, we investigated the functional significance of SAP97 in PV interneurons in layers 2/3 of the visual cortex. PV interneurons expressing SAP97, either endogenously or via exogenous expression, showed distinct membrane properties from those not expressing SAP97. This included an overall decrease in membrane excitability, as indexed by a decrease in membrane resistance and an increase in the stimulus threshold for the first action potential firing. Additionally, SAP97-expressing PV interneurons fired action potentials more frequently and, at moderate stimulus intensities, showed irregular or stuttering firing patterns. Furthermore, SAP97-expressing PV interneurons showed increased glutamatergic input and more extensive dendritic branching when compared with non-expressing PV interneurons. These differences in membrane and synaptic properties would significantly alter how PV interneurons expressing SAP97 compared with those not expressing SAP97 would function in local networks. Thus, our results indicate that the scaffolding protein SAP97 is a critical molecular factor regulating the input-output relationships of cortical PV interneurons.