Layer-Specific Changes in the Prefrontal Glia/Neuron Ratio Characterizes Patches of Gene Expression Disorganization in Children with Autism

Rabelo, Livia Nascimento; Queiroz, José Pablo Gonçalves; Castro, Carla Cristina Miranda; Silva, Sayonara Pereira; Campos, Laura Damasceno; Silva, Larissa Camila; Nascimento, Ezequiel Batista do; Martínez‐Cerdeño, Verónica; Fiuza, Felipe Porto

doi:10.1007/s10803-022-05626-8

Cited by 3 publications

(4 citation statements)

References 47 publications

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“…Intriguingly, this disorganization also involved neurons that did not express Cre, suggesting communication between the Cre-expressing subset of neurons and other layer 5 pyramidal neurons. Further, the patchy disorganization of mouse cortex that we report is reminiscent of the patchy disorganization of cortical tissue observed in children with autism (Rabelo et al, 2022; Stoner et al, 2014).…”

Section: Discussionsupporting

confidence: 67%

“…Indeed, common circuit dysfunctions have been hypothesized to underlie the phenotypic similarities across the heterogeneous mixture of genetic abnormalities associated with these neurodevelopmental disorders (Courchesne and Pierce, 2005; Del Pino et al, 2018; Foss-Feig et al, 2017; Golden et al, 2018; Kaiser and Feng, 2015; Mullins et al, 2016; Robertson and Baron-Cohen, 2017). Further, patches of disorganized cortical tissue have been observed in brains of both children with autism as well as in mouse models of the disorder, around the time of birth (Choi et al, 2016; Dufour et al, 2022; Kim et al, 2017; Orosco et al, 2014; Peñagarikano et al, 2011; Rabelo et al, 2022; Stoner et al, 2014; Yim et al, 2017). However, it remains unknown if mutations in autism-related genes may perturb the development of pyramidal-to-pyramidal neuron circuits during embryonic development.…”

Section: Introductionmentioning

confidence: 99%

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Embryonic cortical layer 5 pyramidal neurons form an active, transient circuit motif perturbed by autism-associated mutations

Munz

Bharioke

Kosche

et al. 2022

Preprint

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Cortical circuits are composed predominantly of pyramidal-to-pyramidal neuron connections, yet their assembly during embryonic development is not well understood. We show that embryonic layer 5 pyramidal neurons, identified through single cell transcriptomics, display two phases of circuit assembly in vivo. At E14.5, a multi-layered circuit motif, composed of a single layer 5 cell type, forms. This motif is transient, switching to a second circuit motif, involving all three types, by E17.5. In vivo targeted single cell recordings and two-photon calcium imaging of embryonic layer 5 neurons reveal that, in both phases, neurons have active somas and neurites, tetrodotoxin-sensitive voltage-gated conductances, and functional glutamatergic synapses. Embryonic layer 5 neurons strongly express autism-associated genes, and perturbing these genes disrupts the switch between the two motifs. Hence, layer 5 pyramidal neurons form transient active pyramidal-to-pyramidal circuits, at the inception of neocortex, and studying these circuits could yield insights into the etiology of autism.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Embryonic cortical layer 5 pyramidal neurons form an active, transient circuit motif perturbed by autism-associated mutations

Munz

Bharioke

Kosche

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Further, the patchy disorganization of mouse cortex that we report is reminiscent of the patchy disorganization of cortical tissue observed in children with autism. 54 , 56 …”

Section: Discussionmentioning

confidence: 99%

“… 16 , 17 , 18 , 19 , 20 , 52 , 53 Further, patches of disorganized cortical tissue have been observed in brains of both children with autism as well as in mouse models of the disorder, around the time of birth. 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 However, it remains unknown if mutations in autism-related genes may perturb the development of PN-to-PN circuits during embryonic development.…”

Section: Introductionmentioning

confidence: 99%

Pyramidal neurons form active, transient, multilayered circuits perturbed by autism-associated mutations at the inception of neocortex

Munz¹,

Bharioke²,

Kosche³

et al. 2023

Cell

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Comment on “Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals”

Herai

Semendeferi

Muotri

2023

Science

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Pinson et al . ( 1 ) concluded that the modern human TKTL1 gene is responsible for an increased number of cortical neurons. We show that the “putative Neanderthal variant” of TKTL1 is present in modern human backgrounds. We dispute their argument that this genetic variant is responsible for brain differences in modern humans as opposed to Neanderthals.

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Layer-Specific Changes in the Prefrontal Glia/Neuron Ratio Characterizes Patches of Gene Expression Disorganization in Children with Autism

Cited by 3 publications

References 47 publications

Embryonic cortical layer 5 pyramidal neurons form an active, transient circuit motif perturbed by autism-associated mutations

Embryonic cortical layer 5 pyramidal neurons form an active, transient circuit motif perturbed by autism-associated mutations

Pyramidal neurons form active, transient, multilayered circuits perturbed by autism-associated mutations at the inception of neocortex

Comment on “Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals”

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