Embryonic cortical layer 5 pyramidal neurons form an active, transient circuit motif perturbed by autism-associated mutations

Munz, M.; Bharioke, A.; Kosche, G.; Moreno-Juan, V.; Brignall, A.; Graff-Meyer, A.; Ulmer, T.; Rodrigues, T.; Haeuselmann, S.; Pavlinic, D.; Ledergerber, N.; Gross-Scherf, B.; Rozsa, B.; Krol, J.; Picelli, S.; Cowan, C. S.; Roska, B.

doi:10.1101/2022.08.31.506080

bioRxiv · 10.1101/2022.08.31.506080

Embryonic cortical layer 5 pyramidal neurons form an active, transient circuit motif perturbed by autism-associated mutations

Munz, M.·Bharioke, A.·Kosche, G.·Moreno-Juan, V.·Brignall, A.·Graff-Meyer, A.·Ulmer, T.·Rodrigues, T.·Haeuselmann, S.·Pavlinic, D.·Ledergerber, N.·Gross-Scherf, B.·Rozsa, B.·Krol, J.·Picelli, S.·Cowan, C. S.·Roska, B.

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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 embryonic layer 5 pyramidal neurons, identified through single cell transcriptomics, display two phases of circuit assembly in vivo. At E14.5, a multi-layered circuit motif, composed of a single layer 5 cell type, forms. This motif is transient, switching to a second circuit motif, involving all three types, by E17.5. In vivo targeted single cell recordings and two-photon calcium imaging of embryonic layer 5 neurons reveal that, in both phases, neurons have active somas and neurites, tetrodotoxin-sensitive voltage-gated conductances, and functional glutamatergic synapses. Embryonic layer 5 neurons strongly express autism-associated genes, and perturbing these genes disrupts the switch between the two motifs. Hence, layer 5 pyramidal neurons form transient active pyramidal-to-pyramidal circuits, at the inception of neocortex, and studying these circuits could yield insights into the etiology of autism.

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Munz, M., Bharioke, A., Kosche, G., Moreno-Juan, V., Brignall, A., Graff-Meyer, A., Ulmer, T., Rodrigues, T., Haeuselmann, S., Pavlinic, D., Ledergerber, N., Gross-Scherf, B., Rozsa, B., Krol, J., Picelli, S., Cowan, C. S., Roska, B.. 2022-08-31. Embryonic cortical layer 5 pyramidal neurons form an active, transient circuit motif perturbed by autism-associated mutations. https://doi.org/10.1101/2022.08.31.506080

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