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Local Connectivity and Synaptic Dynamics in Mouse and Human Neocortex

By Luke Campagnola, Stephanie Seeman, Tom C Chartrand, Lisa Kim, Alex Hoggarth, Clare Gamlin, Shinya Ito, Jessica Trinh, Pasha A Davoudian, Cristina Radaelli, Mean-Hwan Kim, Travis A Hage, Thomas Braun, Lauren Alfiler, Rachel Dalley, Grace Williams, Alex Henry, Alice Mukora, Sara Kebede, David Sandman, Philip Bohn, Julia Andrade, Rachael Larsen, Corinne Teeter, Tanya Daigle, Kyla Berry, Nadia Dotson, Rachel Enstrom, Melissa Gorham, Madie Hupp, Samuel D Lee, Kiet Ngo, Philip R. Nicovich, Lydia Potekhina, Shea Ransford, Jeff Goldy, Delissa McMillen, Trangthanh Pham, Michael Tieu, La'Akea Siverts, Miranda Walker, Colin Farrell, Martin Schroedter, Cliff Slaughterbeck, Charles Cobbs, Richard G Ellenbogen, Ryder P Gwinn, C. Dirk Keene, Andrew L. Ko, Jeffrey Ojemann, Daniel L. Silbergeld, Daniel Carey, Tamara Casper, Kirsten Chrichton, Michael Clark, Nick Dee, Lauren Ellingwood, Jessica Gloe, Matthew Kroll, Josef Sulc, Herman Tung, Katherine Wadhwani, Kristina Brouner, Thomas Egdorf, Amanda Gary, Michelle Maxwell, Medea McGraw, Christina A Pom, Augustin Ruiz, Jasmine Bomben, David Feng, Nika Hejazinia, Shu Shi, Aaron Szafer, Wayne Wakeman, John Philips, Amy Bernard, Luke Esposito, Florence D. D'Orazi, Susan Sunkin, Kimberly Smith, Bosiljka Tasic, Anton Arkhipov, Staci Sorensen, Ed S. Lein, Christof Koch, Gabriel Murphy, Hongkui Zeng, Tim Jarsky

Posted 01 Apr 2021
bioRxiv DOI: 10.1101/2021.03.31.437553

To elucidate cortical microcircuit structure and synaptic properties, we present a unique, extensive, and public synaptic physiology dataset and analysis platform. Through its application, we reveal principles that relate cell type to synapse properties and intralaminar circuit organization in the mouse and human cortex. The dynamics of excitatory synapses align with the postsynaptic cell subclass, whereas inhibitory synapse dynamics partly align with presynaptic cell subclass but with considerable overlap. Despite these associations, synaptic properties are heterogeneous in most subclass to subclass connections. The two main axes of heterogeneity are strength and variability. Cell subclasses divide along the variability axis, while the strength axis accounts for significant heterogeneity within the subclass. In human cortex, excitatory to excitatory synapse dynamics are distinct from those in mouse and short-term plasticity varies with depth across layers 2 and 3. With a novel connectivity analysis that enables fair comparisons between circuit elements, we find that intralaminar connection probability among cell subclasses exhibits a strong layer dependence. These and other findings combined with the analysis platform create new opportunities for the neuroscience community to advance our understanding of cortical microcircuits.

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