Embryonic progenitor pools generate diversity in fine-scale excitatory cortical subnetworks
Ellender TJ., Avery SV., Mahfooz K., Scaber J., von Klemperer A., Nixon SL., Buchan MJ., van Rheede JJ., Gatti A., Waites C., Pavlou HJ., Sims D., Newey SE., Akerman CJ.
<jats:title>Abstract</jats:title><jats:p>The mammalian neocortex is characterized by a variety of neuronal cell types and precise arrangements of synaptic connections, but the processes that generate this diversity are poorly understood. Here we examine how a pool of embryonic progenitor cells consisting of apical intermediate progenitors (aIPs) contribute to diversity within the upper layers of mouse cortex. In utero labeling combined with single-cell RNA-sequencing reveals that aIPs can generate transcriptionally defined glutamatergic cell types, when compared to neighboring neurons born from other embryonic progenitor pools. Whilst sharing layer-associated morphological and functional properties, simultaneous patch clamp recordings and optogenetic studies reveal that aIP-derived neurons exhibit systematic biases in both their intralaminar monosynaptic connectivity and the post-synaptic partners that they target within deeper layers of cortex. Multiple cortical progenitor pools therefore represent an important factor in establishing diversity amongst local and long-range fine-scale glutamatergic connectivity, which generates subnetworks for routing excitatory synaptic information.</jats:p>