Specification of neural circuit architecture shaped by context-dependent patterned LAR-RPTP microexons
Kyung Ah Han,
Taek-Han Yoon,
Jinhu Kim,
Jusung Lee,
Ju Yeon Lee,
Gyubin Jang,
Ji Won Um,
Jong Kyoung Kim and
Jaewon Ko ()
Additional contact information
Kyung Ah Han: Daegu Gyeongbuk Institute of Science and Technology (DGIST)
Taek-Han Yoon: Daegu Gyeongbuk Institute of Science and Technology (DGIST)
Jinhu Kim: Daegu Gyeongbuk Institute of Science and Technology (DGIST)
Jusung Lee: DGIST
Ju Yeon Lee: Korea Basic Science Institute, Research Center for Bioconvergence Analysis
Gyubin Jang: Daegu Gyeongbuk Institute of Science and Technology (DGIST)
Ji Won Um: Daegu Gyeongbuk Institute of Science and Technology (DGIST)
Jong Kyoung Kim: DGIST
Jaewon Ko: Daegu Gyeongbuk Institute of Science and Technology (DGIST)
Nature Communications, 2024, vol. 15, issue 1, 1-21
Abstract:
Abstract LAR-RPTPs are evolutionarily conserved presynaptic cell-adhesion molecules that orchestrate multifarious synaptic adhesion pathways. Extensive alternative splicing of LAR-RPTP mRNAs may produce innumerable LAR-RPTP isoforms that act as regulatory “codes” for determining the identity and strength of specific synapse signaling. However, no direct evidence for this hypothesis exists. Here, using targeted RNA sequencing, we detected LAR-RPTP mRNAs in diverse cell types across adult male mouse brain areas. We found pronounced cell-type–specific patterns of two microexons, meA and meB, in Ptprd mRNAs. Moreover, diverse neural circuits targeting the same neuronal populations were dictated by the expression of different Ptprd variants with distinct inclusion patterns of microexons. Furthermore, conditional ablation of Ptprd meA+ variants at presynaptic loci of distinct hippocampal circuits impaired distinct modes of synaptic transmission and object-location memory. Activity-triggered alterations of the presynaptic Ptprd meA code in subicular neurons mediates NMDA receptor-mediated postsynaptic responses in CA1 neurons and object-location memory. Our data provide the evidence of cell-type- and/or circuit-specific expression patterns in vivo and physiological functions of LAR-RPTP microexons that are dynamically regulated.
Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45695-0
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DOI: 10.1038/s41467-024-45695-0
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