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Embryonic progenitor pools generate diversity in fine-scale excitatory cortical subnetworks.

Tommas J EllenderSophie V AveryKashif MahfoozJakub ScaberAlexander von KlempererSophie L NixonMatthew J BuchanJoram J van RheedeAleksandra GattiCameron WaitesHania J PavlouDavid SimsSarah E NeweyColin J Akerman
Published in: Nature communications (2019)
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.
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