Single-cell RNAseq reveals cell adhesion molecule profiles in electrophysiologically defined neurons

Abstract

In brain, signaling mediated by cell adhesion molecules defines the identity and functional properties of synapses. The specificity of presynaptic and postsynaptic interactions that is presumably mediated by cell adhesion molecules suggests that there exists a logic that could explain neuronal connectivity at the molecular level. Despite its importance, however, the nature of such logic is poorly understood, and even basic parameters, such as the number, identity, and single-cell expression profiles of candidate synaptic cell adhesion molecules, are not known. Here, we devised a comprehensive list of genes involved in cell adhesion, and used single-cell RNA sequencing (RNAseq) to analyze their expression in electrophysiologically defined interneurons and projection neurons. We compared the cell type-specific expression of these genes with that of genes involved in transmembrane ion conductances (i.e., channels), exocytosis, and rho/rac signaling, which regulates the actin cytoskeleton. Using these data, we identified two independent, developmentally regulated networks of interacting genes encoding molecules involved in cell adhesion, exocytosis, and signal transduction. Our approach provides a framework for a presumed cell adhesion and signaling code in neurons, enables correlating electrophysiological with molecular properties of neurons, and suggests avenues toward understanding synaptic specificity.

Diversity of Interneurons in the Dorsal Striatum Revealed by Single-Cell RNA Sequencing and PatchSeq

“…We observed significant electrophysiological differences between cortical and striatal Pvalb -expressing cells that coincided with significantly different levels of expression of genes known to affect those same electrophysiological properties. This provides support to the finding that molecular information correlates with electrophysiological properties (Földy et al., 2016). However, clustering of neurons into subtypes based on transcriptomic data in an unsupervised manner seems to be more powerful with larger separation between groups.…”

Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits

“…Neurexophilins bind to the LNS2 domain of α-neurexins independent of alternative splicing at SS2 (Missler et al, 1998). In situ hybridization and RNAseq data suggest that neurexophilins are adundantly expressed in specific classes of interneurons (e.g., see Földy et al, 2016), but little is known about their functions. Constitutive deletion of neurexophilin-1 caused changes in spontaneous mini-release and in short-term plasticity at inhibitory synapses in the reticular nucleus of the thalamus (Born et al, 2014); these changes were occluded by addition of a GABA B -receptor inhibitor CGP-55845, suggesting that the neurexophilin-1 deletion may have inhibited GABA B -receptor function.…”

Cerebral cortical neuron diversity and development at single-cell resolution

“…Several groups have recently demonstrated the collection and sequencing of RNA from cells following electrophysiological recordings[41–43]. In one study, 45 CCK + interneurons in cortical layer I were first characterized by patch-clamp recording and classified into five subtypes based purely on their electrophysiological properties[41].…”