Adolescent development accelerates responses to input in human neocortical neurons
- 1Stanford University
Abstract
Through childhood and adolescence, profound changes to the physiology of individual neurons accompany large-scale network changes in the mammalian neocortex. These physiological changes are well understood in rodent models but far less is known in the human neocortex. Here we combine patch-clamp electrophysiology and single-cell sequencing (Patch-Seq) in neurosurgically-resected pediatric human brain slices and age-matched mouse brain slices to elucidate the unique developmental trajectory of human neurons. We find that human Layer 2/3 pyramidal neurons show distinctive postnatal changes in neuronal physiology that align with the more directed, feedforward network architecture of human neocortex relative to the mouse. Human-specific changes to spike train dynamics include faster spike latencies and selective acceleration of early spiking. By applying linear modeling to our Patch-Seq data, we identify genes that predict physiological variation across single cells. This unbiased approach unexpectedly identifies BK-type calcium-activated potassium channels as key drivers of human postnatal changes in spike train dynamics between childhood and adolescence. We further test this pathway through pharmacology and computational modeling. Together, our results reveal novel mechanisms of postnatal maturation in human neocortical neurons and demonstrate a new application of Patch-Seq to uncover gene-physiology relationships at single-cell resolution.
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BibTeX
@misc{owen2026adolescent,
title = {{Adolescent development accelerates responses to input in human neocortical neurons}},
author = {S. F. Owen and R. M. Kendrick and J. K. Clark and E. P. Leonard and N. Ramasamy and S. S. DeLope and H. W. Phillips and V. P. Buch and K. B. Mahaney and G. A. Grant and L. M. Prolo},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.16.746058},
url = {https://www.biorxiv.org/content/10.64898/2026.09.16.746058v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Adolescent development accelerates responses to input in human neocortical neurons
AU - S. F. Owen
AU - R. M. Kendrick
AU - J. K. Clark
AU - E. P. Leonard
AU - N. Ramasamy
AU - S. S. DeLope
AU - H. W. Phillips
AU - V. P. Buch
AU - K. B. Mahaney
AU - G. A. Grant
AU - L. M. Prolo
PY - 2026
DA - 2026/09/16
PB - bioRxiv
DO - 10.64898/2026.09.16.746058
UR - https://www.biorxiv.org/content/10.64898/2026.09.16.746058v1
AB - Through childhood and adolescence, profound changes to the physiology of individual neurons accompany large-scale network changes in the mammalian neocortex. These physiological changes are well understood in rodent models but far less is known in the human neocortex. Here we combine patch-clamp electrophysiology and single-cell sequencing (Patch-Seq) in neurosurgically-resected pediatric human brain slices and age-matched mouse brain slices to elucidate the unique developmental trajectory of human neurons. We find that human Layer 2/3 pyramidal neurons show distinctive postnatal changes in neuronal physiology that align with the more directed, feedforward network architecture of human neocortex relative to the mouse. Human-specific changes to spike train dynamics include faster spike latencies and selective acceleration of early spiking. By applying linear modeling to our Patch-Seq data, we identify genes that predict physiological variation across single cells. This unbiased approach unexpectedly identifies BK-type calcium-activated potassium channels as key drivers of human postnatal changes in spike train dynamics between childhood and adolescence. We further test this pathway through pharmacology and computational modeling. Together, our results reveal novel mechanisms of postnatal maturation in human neocortical neurons and demonstrate a new application of Patch-Seq to uncover gene-physiology relationships at single-cell resolution.
ER -