Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex.
Publication Title
Science
Document Type
Article
Publication Date
10-13-2023
Keywords
washington; swedish; swedish neurosci; Animals; Humans; Mice; Axons; Interneurons; Neocortex; Pyramidal Cells; Transcriptome
Abstract
Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1. Subclass and subtype comparisons showed stronger transcriptomic differences in human L1 and were correlated with strong morphoelectric variability along dimensions distinct from mouse L1 variability. Accompanied by greater layer thickness and other cytoarchitecture changes, these findings suggest that L1 has diverged in evolution, reflecting the demands of regulating the expanded human neocortical circuit.
Clinical Institute
Neurosciences (Brain & Spine)
Specialty/Research Institute
Neurosciences
DOI
10.1126/science.adf0805
