ArticleThe American journal of psychiatry2024
Cell Type-Specific Profiles and Developmental Trajectories of Transcriptomes in Primate Prefrontal Layer 3 Pyramidal Neurons: Implications for Schizophrenia.
Article in The American journal of psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Dorsolateral Prefrontal Cortex Circuitry at the Intersection of Cognition and Disease.Biological psychiatry · 2026Review
- Mapping spatially organized molecular and genetic signatures of schizophrenia across multiple scales in human prefrontal cortex.bioRxiv : the preprint server for biology · 2026Article
- Selective recognition memory impairment in mitochondrial hydroxylase Clk1 mutant mice, rescued by antipsychotics.Acta pharmacologica Sinica · 2026Article
- Characterizing the Most Vulnerable Prefrontal Cortical Neurons in Schizophrenia.The American journal of psychiatry · 2024Article
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4 authors.
Funding
Abstract
objectiveIn schizophrenia, impaired working memory is associated with transcriptome alterations in layer 3 pyramidal neurons (L3PNs) in the dorsolateral prefrontal cortex (DLPFC). Distinct subtypes of L3PNs that send axonal projections to the DLPFC in the opposite hemisphere (callosal projection [CP] neurons) or the parietal cortex in the same hemisphere (ipsilateral projection [IP] neurons) play critical roles in working memory. However, how the transcriptomes of these L3PN subtypes might shift during late postnatal development when working memory impairments emerge in individuals later diagnosed with schizophrenia is not known. The aim of this study was to characterize and compare the transcriptome profiles of CP and IP L3PNs across developmental transitions from prepuberty to adulthood in macaque monkeys.
methodsThe authors used retrograde labeling to identify CP and IP L3PNs in the DLPFC of prepubertal, postpubertal, and adult macaque monkeys, and used laser microdissection to capture these neurons for RNA sequencing.
resultsAt all three ages, CP and IP L3PNs had distinct transcriptomes, with the number of genes differentially expressed between neuronal subtypes increasing with age. For IP L3PNs, age-related shifts in gene expression were most prominent between prepubertal and postpubertal animals, whereas for CP L3PNs such shifts were most prominent between postpubertal and adult animals.
conclusionsThese findings demonstrate the presence of cell type-specific profiles and developmental trajectories of the transcriptomes of PPC-projecting IP and DLPFC-projecting CP L3PNs in monkey DLPFC. The evidence that IP L3PNs reach a mature transcriptome earlier than CP L3PNs suggests that these two subtypes differentially contribute to the maturation of working memory performance across late postnatal development and that they may be differentially vulnerable to the disease process of schizophrenia at specific stages of postnatal development.
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