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

Kim, M.-H.; Radaelli, Cristina; Thomsen, Elliot R.; Mahoney, Joseph T.; Long, Brian; Taormina, Michael J.; Kebede, Sara; Gamlin, Clare; Sorensen, Staci A.; Campagnola, Luke; Dee, Nick; D’Orazi, Florence D.; Ojemann, Jeffrey G.; Silbergeld, Daniel L.; Gwinn, Ryder P.; Cobbs, Charles; Keene, C. Dirk; Jarsky, Tim; Murphy, Gabe J.; Zeng, Hongkui; Nicovich, Philip R.; Ting, Jonathan T.; Lein, Ed

doi:10.1101/2020.10.16.343343

Cited by 6 publications

(6 citation statements)

References 111 publications

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“…Also, BAR-seq was originally designed to use ISS for axon tracing by sequencing neuron-specific barcodes introduced by a virus injected into the brain, but was later adapted to sequence gene barcodes 64 as well. In addition, while not an -ome per se, electrophysiology has been recorded prior to transcriptome profiling in the same cells, such as with a patch-clamp in explanted human neurons, followed by HCR-smFISH 84 , and with extracellular electrodes in cultured cardiomyocytes, followed by STARmap in electro-seq 85 .…”

Section: Multi-omicsmentioning

confidence: 99%

Museum of spatial transcriptomics

2022

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The function of many biological systems, such as embryos, liver lobules, intestinal villi, and tumors, depends on the spatial organization of their cells. In the past decade, high-throughput technologies have been developed to quantify gene expression in space, and computational methods have been developed that leverage spatial gene expression data to identify genes with spatial patterns and to delineate neighborhoods within tissues. To comprehensively document spatial gene expression technologies and data-analysis methods, we present a curated review of literature on spatial transcriptomics dating back to 1987, along with a thorough analysis of trends in the field, such as usage of experimental techniques, species, tissues studied, and computational approaches used. Our Review places current methods in a historical context, and we derive insights about the field that can guide current research strategies. A companion supplement offers a more detailed look at the technologies and methods analyzed: https://pachterlab.github.io/LP_2021/.

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Section: Multi-omicsmentioning

confidence: 99%

Museum of spatial transcriptomics

2022

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“…While RAI1 expression profiles are similar in adult mice and marmosets, in newborn marmosets, RAI1 is detected in significantly fewer neurons, specifically excitatory but not inhibitory neurons. Comparative analyses found highly similar proportions of inhibitory neuronal subclasses and connectivity in mice, marmoset, and human cortices (Bakken et al., 2021; Kim et al., 2023). By contrast, glutamatergic neurons in humans and marmosets share more markers with each other than with mice (Bakken et al., 2021).…”

Section: Discussionmentioning

confidence: 99%

Comparative analyses of the Smith−Magenis syndrome protein RAI1 in mice and common marmoset monkeys

Chang,

Lee,

Haque

et al. 2024

J of Comparative Neurology

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Retinoic acid‐induced 1 (RAI1) encodes a transcriptional regulator critical for brain development and function. RAI1 haploinsufficiency in humans causes a syndromic autism spectrum disorder known as Smith−Magenis syndrome (SMS). The neuroanatomical distribution of RAI1 has not been quantitatively analyzed during the development of the prefrontal cortex, a brain region critical for cognitive function and social behaviors and commonly implicated in autism spectrum disorders, including SMS. Here, we performed comparative analyses to uncover the evolutionarily convergent and divergent expression profiles of RAI1 in major cell types during prefrontal cortex maturation in common marmoset monkeys (Callithrix jacchus) and mice (Mus musculus). We found that while RAI1 in both species is enriched in neurons, the percentage of excitatory neurons that express RAI1 is higher in newborn mice than in newborn marmosets. By contrast, RAI1 shows similar neural distribution in adult marmosets and adult mice. In marmosets, RAI1 is expressed in several primate‐specific cell types, including intralaminar astrocytes and MEIS2‐expressing prefrontal GABAergic neurons. At the molecular level, we discovered that RAI1 forms a protein complex with transcription factor 20 (TCF20), PHD finger protein 14 (PHF14), and high mobility group 20A (HMG20A) in the marmoset brain. In vitro assays in human cells revealed that TCF20 regulates RAI1 protein abundance. This work demonstrates that RAI1 expression and protein interactions are largely conserved but with some unique expression in primate‐specific cells. The results also suggest that altered RAI1 abundance could contribute to disease features in disorders caused by TCF20 dosage imbalance.

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“…Given that human neurons differ in various ways from their counterparts in rodents (Chameh et al, 2023; de Kock and Feldmeyer, 2023; Eyal et al, 2016; Gidon et al, 2020; Kalmbach et al, 2018; Kim et al, 2023; Lee et al, 2023; Libe-Philippot et al, 2023; Molnar et al, 2016; Szegedi et al, 2023; Testa-Silva et al, 2022; Testa-Silva et al, 2014; Wilbers et al, 2023), it is highly relevant to study human cells directly. The life span of humans is significantly longer than that of rodents, and because neurons do not divide in the neocortex once they are generated, it is important to understand how the same cell types survive aging in humans who live 20–30 times longer than rodents do.…”

Section: Discussionmentioning

confidence: 99%

Aging-associated weakening of the action potential in fast-spiking interneurons in the human neocortex

Szegedi,

Tiszlavicz,

Furdan

et al. 2024

Preprint

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Aging is associated with the slowdown of neuronal processing and cognitive performance in the brain; however, the exact cellular mechanisms behind this deterioration in humans are poorly elucidated. Recordings in human acute brain slices prepared from tissue resected during brain surgery enable the investigation of neuronal changes with age. Although neocortical fast-spiking cells are widely implicated in neuronal network activities underlying cognitive processes, they are vulnerable to neurodegeneration. Herein, we analyzed the electrical properties of 147 fast-spiking interneurons in neocortex samples resected in brain surgery from 106 patients aged 11–84 years. By studying the electrophysiological features of action potentials and passive membrane properties, we report that action potential overshoot significantly decreases and spike half-width increases with age. Moreover, the action potential maximum-rise speed (but not the repolarization speed or the afterhyperpolarization amplitude) significantly changed with age, suggesting a particular weakening of the sodium channel current generated in the soma. Cell passive membrane properties measured as the input resistance, membrane time constant, and cell capacitance remained unaffected by senescence. Thus, we conclude that the action potential in fast-spiking interneurons shows a significant weakening in the human neocortex with age. This may contribute to the deterioration of cortical functions by aging.

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

Cited by 6 publications

References 111 publications

Museum of spatial transcriptomics

Museum of spatial transcriptomics

Comparative analyses of the Smith−Magenis syndrome protein RAI1 in mice and common marmoset monkeys

Aging-associated weakening of the action potential in fast-spiking interneurons in the human neocortex

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