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Cell-type-selective synaptogenesis during the development of layer 6 corticothalamic neuron connectivity in the mammalian neocortex

The function of the mammalian neocortex relies on the timing of axon extension and establishment of cell-type-biased patterns of excitatory synaptic connections. A subtype of excitatory neurons, layer 6 corticothalamic neurons (L6CThNs), ultimately exhibits a marked preference for synapsing onto par...

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Main Authors: Gutman-Wei, Alan (Author) , Sudarsanam, Sriram (Author) , Cabalinan, Alec G. (Author) , Shahid, Naseer (Author) , Shi, Anny (Author) , Guzman-Clavel, Luis E. (Author) , Spindler-Krage, Sophia M. (Author) , Agarwal, Amit (Author) , Kolodkin, Alex L. (Author) , Brown, Solange P. (Author)
Format: Article (Journal)
Language:English
Published: 27 January 2026
In: Cell reports
Year: 2026, Volume: 45, Issue: 1, Pages: 1-14
ISSN:2211-1247
DOI:10.1016/j.celrep.2025.116792
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.celrep.2025.116792
Verlag, kostenfrei, Volltext: https://www.cell.com/cell-reports/abstract/S2211-1247(25)01564-5
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Author Notes:Alan Y. Gutman-Wei, Sriram Sudarsanam, Alec G. Cabalinan, Naseer Shahid, Anny Shi, Luis E. Guzman-Clavel, Sophia M. Spindler-Krage, Amit Agarwal, Alex L. Kolodkin, and Solange P. Brown
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Summary:The function of the mammalian neocortex relies on the timing of axon extension and establishment of cell-type-biased patterns of excitatory synaptic connections. A subtype of excitatory neurons, layer 6 corticothalamic neurons (L6CThNs), ultimately exhibits a marked preference for synapsing onto parvalbumin-positive (PV) inhibitory interneurons over more common excitatory cells in layers 6 and 4 (L6, L4). We show that the intracortical axons of L6CThNs develop in phases, first elongating within L6, then pausing before extending translaminar branches into L4. Decreasing L6CThN excitability selectively enhances axon growth in L6 but not the later elaboration in L4. For both layers, we test whether preferential synaptogenesis onto rarer PV interneurons, or non-selective synapse formation followed by selective pruning, generates adult connectivity. We find that L6CThNs form functional AMPA-receptor-containing synapses preferentially onto PV interneurons. Silent L6CThN synapses are not detected. Our findings show that cell-type-biased synaptogenesis underlies the formation of functional cell-type-specific excitatory connections in the neocortex.
Item Description:Gesehen am 07.04.2026
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2025.116792

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