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Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex

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 obtai...

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Autores principales: Kim, Mean-Hwan, Radaelli, Cristina, Thomsen, Elliot R, Monet, Deja, Chartrand, Thomas, Jorstad, Nikolas L, Mahoney, Joseph T, Taormina, Michael J, Long, Brian, Baker, Katherine, Bakken, Trygve E, Campagnola, Luke, Casper, Tamara, Clark, Michael, Dee, Nick, D'Orazi, Florence, Gamlin, Clare, Kalmbach, Brian E, Kebede, Sara, Lee, Brian R, Ng, Lindsay, Trinh, Jessica, Cobbs, Charles, Gwinn, Ryder P, Keene, C Dirk, Ko, Andrew L, Ojemann, Jeffrey G, Silbergeld, Daniel L, Sorensen, Staci A, Berg, Jim, Smith, Kimberly A, Nicovich, Philip R, Jarsky, Tim, Zeng, Hongkui, Ting, Jonathan T, Levi, Boaz P, Lein, Ed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10332811/
https://www.ncbi.nlm.nih.gov/pubmed/37249212
http://dx.doi.org/10.7554/eLife.81863
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author Kim, Mean-Hwan
Radaelli, Cristina
Thomsen, Elliot R
Monet, Deja
Chartrand, Thomas
Jorstad, Nikolas L
Mahoney, Joseph T
Taormina, Michael J
Long, Brian
Baker, Katherine
Bakken, Trygve E
Campagnola, Luke
Casper, Tamara
Clark, Michael
Dee, Nick
D'Orazi, Florence
Gamlin, Clare
Kalmbach, Brian E
Kebede, Sara
Lee, Brian R
Ng, Lindsay
Trinh, Jessica
Cobbs, Charles
Gwinn, Ryder P
Keene, C Dirk
Ko, Andrew L
Ojemann, Jeffrey G
Silbergeld, Daniel L
Sorensen, Staci A
Berg, Jim
Smith, Kimberly A
Nicovich, Philip R
Jarsky, Tim
Zeng, Hongkui
Ting, Jonathan T
Levi, Boaz P
Lein, Ed
author_facet Kim, Mean-Hwan
Radaelli, Cristina
Thomsen, Elliot R
Monet, Deja
Chartrand, Thomas
Jorstad, Nikolas L
Mahoney, Joseph T
Taormina, Michael J
Long, Brian
Baker, Katherine
Bakken, Trygve E
Campagnola, Luke
Casper, Tamara
Clark, Michael
Dee, Nick
D'Orazi, Florence
Gamlin, Clare
Kalmbach, Brian E
Kebede, Sara
Lee, Brian R
Ng, Lindsay
Trinh, Jessica
Cobbs, Charles
Gwinn, Ryder P
Keene, C Dirk
Ko, Andrew L
Ojemann, Jeffrey G
Silbergeld, Daniel L
Sorensen, Staci A
Berg, Jim
Smith, Kimberly A
Nicovich, Philip R
Jarsky, Tim
Zeng, Hongkui
Ting, Jonathan T
Levi, Boaz P
Lein, Ed
author_sort Kim, Mean-Hwan
collection PubMed
description 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.
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spelling pubmed-103328112023-07-11 Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex Kim, Mean-Hwan Radaelli, Cristina Thomsen, Elliot R Monet, Deja Chartrand, Thomas Jorstad, Nikolas L Mahoney, Joseph T Taormina, Michael J Long, Brian Baker, Katherine Bakken, Trygve E Campagnola, Luke Casper, Tamara Clark, Michael Dee, Nick D'Orazi, Florence Gamlin, Clare Kalmbach, Brian E Kebede, Sara Lee, Brian R Ng, Lindsay Trinh, Jessica Cobbs, Charles Gwinn, Ryder P Keene, C Dirk Ko, Andrew L Ojemann, Jeffrey G Silbergeld, Daniel L Sorensen, Staci A Berg, Jim Smith, Kimberly A Nicovich, Philip R Jarsky, Tim Zeng, Hongkui Ting, Jonathan T Levi, Boaz P Lein, Ed eLife Neuroscience 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. eLife Sciences Publications, Ltd 2023-05-30 /pmc/articles/PMC10332811/ /pubmed/37249212 http://dx.doi.org/10.7554/eLife.81863 Text en © 2023, Kim et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Kim, Mean-Hwan
Radaelli, Cristina
Thomsen, Elliot R
Monet, Deja
Chartrand, Thomas
Jorstad, Nikolas L
Mahoney, Joseph T
Taormina, Michael J
Long, Brian
Baker, Katherine
Bakken, Trygve E
Campagnola, Luke
Casper, Tamara
Clark, Michael
Dee, Nick
D'Orazi, Florence
Gamlin, Clare
Kalmbach, Brian E
Kebede, Sara
Lee, Brian R
Ng, Lindsay
Trinh, Jessica
Cobbs, Charles
Gwinn, Ryder P
Keene, C Dirk
Ko, Andrew L
Ojemann, Jeffrey G
Silbergeld, Daniel L
Sorensen, Staci A
Berg, Jim
Smith, Kimberly A
Nicovich, Philip R
Jarsky, Tim
Zeng, Hongkui
Ting, Jonathan T
Levi, Boaz P
Lein, Ed
Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex
title Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex
title_full Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex
title_fullStr Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex
title_full_unstemmed Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex
title_short Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex
title_sort target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10332811/
https://www.ncbi.nlm.nih.gov/pubmed/37249212
http://dx.doi.org/10.7554/eLife.81863
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