Progress toward defining the molecular identities of neocortical neurons

Abstract

"The neurons that make up the human cerebral cortex are responsible for a wide array of higher cognitive, social-emotional, sensory and motor functions. These very complex functions are supported by a rich diversity of excitatory and inhibitory neurons, each of which has its own developmental pathway, and is specifically assembled into highly complex cortical circuits with powerful computational capacities. Recent studies using single-cell transcriptomics, single-cell electrophysiological recordings, and morphological reconstruction have begun to reveal surprising levels of neuronal diversity in mammals, defined by distinctive transcriptomic signatures, morphological, and physiological phenotypes. While most of the available data rely on studies performed on mouse neocortex, several recent findings in the human neocortex point to both conserved molecular profiles, and human-specific differences. Herein, the main milestones in the classification of neocortical neurons are discussed, beginning with the “classical” combination of a few class-specific marker expression and cell morphologies, and progressing to their origin and recent multiplex profiling. While single-cell and single-nucleus RNA sequencing data provide a huge progress in neuronal taxonomy, the boundaries between subclasses can be defined and validated only in combination with morphological and electrophysiological features. "