AUTHORS
Martin Munz, Arjun Bharioke, Georg Kosche, Verónica Moreno-Juan, Alexandra Brignall, Tiago M Rodrigues, Alexandra Graff-Meyer, Talia Ulmer, Stephanie Haeuselmann, Dinko Pavlinic, Nicole Ledergerber, Brigitte Gross-Scherf, Balázs Rózsa, Jacek Krol, Simone Picelli, Cameron S Cowan, Botond Roska
Cell. 2023 Apr 27;186(9):1930-1949.e31. doi: 10.1016/j.cell.2023.03.025. Epub 2023 Apr 17.
ABSTRACT
Cortical circuits are composed predominantly of pyramidal-to-pyramidal neuron connections, yet their assembly during embryonic development is not well understood. We show that mouse embryonic Rbp4-Cre cortical neurons, transcriptomically closest to layer 5 pyramidal neurons, display two phases of circuit assembly in vivo. At E14.5, they form a multi-layered circuit motif, composed of only embryonic near-projecting-type neurons. By E17.5, this transitions to a second motif involving all three embryonic types, analogous to the three adult layer 5 types. In vivo patch clamp recordings and two-photon calcium imaging of embryonic Rbp4-Cre neurons reveal active somas and neurites, tetrodotoxin-sensitive voltage-gated conductances, and functional glutamatergic synapses, from E14.5 onwards. Embryonic Rbp4-Cre neurons strongly express autism-associated genes and perturbing these genes interferes with the switch between the two motifs. Hence, pyramidal neurons form active, transient, multi-layered pyramidal-to-pyramidal circuits at the inception of neocortex, and studying these circuits could yield insights into the etiology of autism.
PMID:37071993 | PMC:PMC10156177 | DOI:10.1016/j.cell.2023.03.025
