Isochronic development of cortical synapses in primates and mice

Wildenberg, Gregg; Li, Hanyu; Sampathkumar, Vandana; Sorokina, Anastasia; Kasthuri, Narayanan

doi:10.6082/j8xaz-smj06

Published December 4, 2023 | Version v1

Journal article Open

Isochronic development of cortical synapses in primates and mice

1. University of Chicago

The neotenous, or delayed, development of primate neurons, particularly human ones, is thought to underlie primate-specific abilities like cognition. We tested whether synaptic development follows suit—would synapses, in absolute time, develop slower in longer-lived, highly cognitive species like non-human primates than in shorter-lived species with less human-like cognitive abilities, e.g., the mouse? Instead, we find that excitatory and inhibitory synapses in the male Mus musculus (mouse) and Rhesus macaque (primate) cortex form at similar rates, at similar times after birth. Primate excitatory and inhibitory synapses and mouse excitatory synapses also prune in such an isochronic fashion. Mouse inhibitory synapses are the lone exception, which are not pruned and instead continuously added throughout life. The monotony of synaptic development clocks across species with disparate lifespans, experiences, and cognitive abilities argues that such programs are likely orchestrated by genetic events rather than experience.

Data availability

All original EM data for V1 are freely available online at: https://bossdb.org/project/wildenberg2023 or DOI:10.60533/boss-2023-0s41. Mouse S1 datasets that we analyzed for changes in excitatory synapses are available at their original publication which can be found at: https://pubmed.ncbi.nlm.nih.gov/33273061/. Mouse p60, S1 excitatory synapse measurements were manually analyzed using the publicly available neuroglancer file from which can be found here: https://github.com/google/neuroglancer. Mouse p36 datasets are publicly available here for L2/3: https://www.microns-explorer.org/phase1 and here for, p87, L4: https://www.microns-explorer.org/cortical-mm3. Automatic segmentation of neurons, synapses and mitochondria of mouse V1, L4 p14 and p105 are available as a WebKnossos format for further public proofreading/error checking. For Figs. 1–3, source data can be found in the source data Excel file. All other source data (i.e., Fig. 4 and Supplementary Figs. 7–11) can be found here: https://bossdb.org/project/wildenberg2023. Source data are provided with this paper.

Homemade code used for EM image processing (i.e., 2D stitching, 3D alignments, brightness, and contrast normalization) can be freely accessed here: https://github.com/Hanyu-Li/klab_utils or https://doi.org/10.5072/zenodo.1246118 3D alignment was performed using the publicly available Aligntk software available here: https://mmbios.pitt.edu/aligntk-home. Homemade code used for data analysis of Knossos traced skeletons (i.e., XML files) can be freely accessed here: https://github.com/knorwood0/MNRVA or https://doi.org/10.5072/zenodo.1246116108. An extensive description of all automatic segmentation details can be found here: https://knowledge.uchicago.edu/record/3579?ln=en and see Supplementary Fig. 5.

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