Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex
- Allen Institute for Brain Science, United States
- Swedish Neuroscience Institute, United States
- University of Washington, United States
Abstract
Rodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not been well investigated in human cortex, where there are major technical challenges in reliably obtaining healthy tissue, conducting multiple patch-clamp recordings on inhibitory cell types, and identifying those cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings, post-hoc fluorescent in situ hybridization (FISH), machine learning-based cell type classification and prospective GABAergic AAV-based labeling to investigate synaptic properties between pyramidal neurons and PVALB- vs. SST-positive interneurons. We find that there are robust molecular differences in synapse-associated genes between these neuron types, and that individual presynaptic pyramidal neurons evoke postsynaptic responses with heterogeneous synaptic dynamics in different postsynaptic cell types. Using molecular identification with FISH and classifiers based on transcriptomically identified PVALB neurons analyzed by Patch-seq, we find that PVALB neurons typically show depressing synaptic characteristics, whereas other interneuron types including SST-positive neurons show facilitating characteristics. Together, these data support the existence of target cell-specific synaptic properties in human cortex that are similar to rodent, thereby indicating evolutionary conservation of local circuit connectivity motifs from excitatory to inhibitory neurons and their synaptic dynamics.
Data availability
Single nucleus transcriptomic datasets from human MTG (Hodge et al., 2019) and mouse VISp (Tasic et al., 2018) are available in the Allen Institute website (https://portal.brain-map.org/atlases-and-data/rnaseq). Synaptic connectivity assay datasets including raw traces and related metadata information with MATLAB files (.mat), classifier analysis codes, and their intrinsic membrane property values are available in the DRYAD repository (doi:10.5061/dryad.jdfn2z3dm). Synaptic physiology experimental protocols and related topics are also available in the Allen Institute website (https://portal.brain-map.org/explore/connectivity/synaptic-physiology). To provide more publicly accessible data format, Neurodata Without Borders (NWB) files for synaptic connectivity assay performed in this study and human single cell patch-seq experimental data will be also available soon at DANDI or the BICCN data catalog.
Article and author information
Author details
Funding
NIH BRAIN Initiative (1RF1MH114126-01)
- Jonathan T Ting
- Boaz P. Levi
- Ed Lein
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sacha B Nelson, Brandeis University, United States
Version history
- Preprint posted: October 17, 2020 (view preprint)
- Received: July 14, 2022
- Accepted: May 29, 2023
- Accepted Manuscript published: May 30, 2023 (version 1)
- Version of Record published: July 10, 2023 (version 2)
Copyright
© 2023, Kim et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex
eLife 12:e81863.
https://doi.org/10.7554/eLife.81863
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