A Hierarchical Structure of Cortical Interneuron Electrical Diversity Revealed by Automated Statistical Analysis

Although the diversity of cortical interneuron electrical properties is well recognized, the number of distinct electrical types (e-types) is still a matter of debate. Recently, descriptions of interneuron variability were standardized by multiple laboratories on the basis of a subjective classification scheme as set out by the Petilla convention (Petilla Interneuron Nomenclature Group, PING). Here, we present a quantitative, statistical analysis of a database of nearly five hundred neurons manually annotated according to the PING nomenclature. For each cell, 38 features were extracted from responses to suprathreshold current stimuli and statistically analyzed to examine whether cortical interneurons subdivide into e-types. We showed that the partitioning into different e-types is indeed the major component of data variability. The analysis suggests refining the PING e-type classification to be hierarchical, whereby most variability is first captured within a coarse subpartition, and then subsequently divided into finer subpartitions. The coarse partition matches the well-known partitioning of interneurons into fast spiking and adapting cells. Finer subpartitions match the burst, continuous, and delayed subtypes. Additionally, our analysis enabled the ranking of features according to their ability to differentiate among e-types. We showed that our quantitative e-type assignment is more than 90 accurate and manages to catch several human errors.