Multiomic foundations of human prefrontal cortex tissue function

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.