Abstract:
Although its dense connections with other brain areas suggests that the claustrum is involved in higher-order brain functions, little is known about the properties of claustrum neurons. Using whole-cell patch clamp recordings in acute brain slices of mice, we characterized the intrinsic electrical properties of more than 300 claustral neurons and used unsupervised clustering of these properties to define distinct cell types. Differences in intrinsic properties permitted separation of interneurons (INs) from projection neurons (PNs). Five subtypes of PNs could be further identified by differences in their adaptation of action potential (AP) frequency and amplitude, as well as their AP firing variability. Injection of retrogradely transported fluorescent beads revealed that PN subtypes differed in their projection targets: one projected solely to subcortical areas while three out of the remaining four targeted cortical areas. INs expressing parvalbumin (PV), somatostatin (SST), or vasoactive intestinal peptide (VIP) formed a heterogenous group. PV-INs were readily distinguishable from VIP-INs and SST-INs, while the latter two were clustered together. To distinguish IN subtypes, an artificial neural network was trained to distinguish the properties of PV-INs, SST-INs, and VIP-INs, as independently identified through their expression of marker proteins. A user-friendly, machine-learning tool that uses intrinsic electrical properties to distinguish these eight different types of claustral cells was developed to facilitate implementation of our classification scheme. Systematic classification of claustrum neurons lays the foundation for future determinations of claustrum circuit function, which will advance our understanding of the role of the claustrum in brain function.
摘要:
尽管它与其他大脑区域的紧密连接表明caustrum参与了更高级的大脑功能,人们对锁骨神经元的特性知之甚少。使用全细胞膜片钳记录小鼠急性脑切片,我们表征了300多个claustral神经元的固有电特性,并使用这些特性的无监督聚类来定义不同的细胞类型。内在性质的差异允许中间神经元(IN)与投射神经元(PN)分离。通过对动作电位(AP)频率和振幅的适应性差异,可以进一步确定PN的五个亚型。以及他们的AP射击可变性。逆行传输的荧光珠的注射表明,PN亚型的投射目标不同:一个仅投射到皮质下区域,而其余四个目标皮质区域中有三个。INs表达小白蛋白(PV),生长抑素(SST),或血管活性肠肽(VIP)形成异源性基团。PV-INs很容易与VIP-INs和SST-INs区分开来,而后两者聚集在一起。为了区分IN亚型,训练人工神经网络来区分PV-IN的属性,SST-IN,和VIP-IN,通过其标记蛋白的表达独立鉴定。一个用户友好的,机器学习工具,使用固有的电特性来区分这八种不同类型的claustral细胞开发,以促进我们的分类方案的实施。锁骨神经元的系统分类为未来确定锁骨电路功能奠定了基础,这将提高我们对caustrum在大脑功能中的作用的理解。