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Multiomic foundations of human prefrontal cortex tissue function.

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    This study reveals a "transcriptional program associated with neurotransmission" (TPAWN) in living human prefrontal cortex (PFC) tissue. TPAWN links RNA expression to brain function, offering new insights into higher-order cognitive processes.

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    Area of Science:

    • Neuroscience
    • Genomics
    • Molecular Biology

    Background:

    • The prefrontal cortex (PFC) governs higher-order functions, but its molecular underpinnings are poorly understood, especially using postmortem tissue.
    • Investigating the multiomic foundations of PFC function in living individuals is crucial for advancing brain science.

    Approach:

    • Analyzed RNA transcript expression in PFC samples from living participants, correlating it with real-time neurotransmission.
    • Compared multiomic data from living PFC tissue with postmortem samples to identify differences.
    • Identified a specific RNA signature, the
    • transcriptional program associated with neurotransmission
    • (TPAWN), linked to neurotransmission and higher-order brain functions.

    Key Points:

    • TPAWN, identified in living PFC, associates RNA expression with neurotransmitter activity (dopamine, serotonin, norepinephrine).
    • TPAWN genes are evolutionarily conserved and implicated in higher-order brain functions, distinct from common genetic variants.
    • Significant multiomic differences exist between living and postmortem PFC tissue, affecting RNA and protein expression and splicing.

    Conclusions:

    • Studies using living human brain tissue provide a more accurate view of PFC molecular foundations.
    • The findings highlight the importance of studying brain function in vivo to understand complex cognitive processes.
    • This research advances the understanding of the multiomic basis of human cognition and behavior.