TY - JOUR T1 - Identification of mouse claustral neuron types based on their intrinsic electrical properties JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0216-20.2020 SP - ENEURO.0216-20.2020 AU - Martin Graf AU - Aditya Nair AU - Kelly L.L Wong AU - Yanxia Tang AU - George J. Augustine Y1 - 2020/06/10 UR - http://www.eneuro.org/content/early/2020/06/10/ENEURO.0216-20.2020.abstract N2 - 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 (IN) from projection neurons (PN). Five subtypes of PN 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 3 out of the remaining 4 targeted cortical areas. IN expressing parvalbumin (PV), somatostatin (SST) or vasoactive-intestinal peptide (VIP) formed a heterogenous group. PV-IN were readily distinguishable from VIP-IN and SST-IN, while the latter two were clustered together. To distinguish IN subtypes, an artificial neural network was trained to distinguish the properties of PV-IN, SST-IN and VIP-IN, as independently identified through their expression of marker proteins. A user-friendly, machine-learning tool that uses intrinsic electrical properties to distinguish these 8 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.Significance statement The function of the claustrum is mysterious. To better understand the claustrum, we examined the electrical properties of its neurons and identified 8 neuron types. Differences in properties permitted clear separation of interneurons (IN) from projection neurons (PN). PN could be further subdivided based on differences in their physiological and anatomical characteristics. Although IN were heterogenous, a computational neural network could distinguish several subtypes. Our work is the first comprehensive analysis of claustrum neurons and provides important information about the physiological properties of these neurons. This work lays the foundation for advancing our understanding of signal processing within the claustrum and, thereby, elucidating how the claustrum contributes to brain information processing. ER -