Researchers Identify Distinct and Reproducible Gene Expression Program Associated with Neurotransmission in the Living Human Brain

This discovery provides insights into the molecular mechanisms that support human cognition, emotion, and behavior. The findings were published on February 19 in Molecular Psychiatry.

Background

Neurotransmission, which involves the electrical and chemical signaling between neurons, is essential for all brain function. Previous gene expression studies on the human brain typically relied on postmortem tissue, which limited understanding of genes actively involved in real-time neuronal communication.

Study Methodology and Findings

Investigators integrated gene expression profiling from the prefrontal cortex with direct intracranial measures of neurotransmission. These measures were collected from over 100 individuals during neurosurgical procedures. By combining molecular data with real-time physiological recordings, the team identified a coordinated set of genes whose activity correlates with neuronal signaling, representing a transcriptional program associated with neurotransmission.

Expert Commentary

Dr. Alexander Charney, Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, stated that these findings represent a significant advancement in the ability to study living brain biology.

"This work allows for the examination of the molecular architecture of neurotransmission as it occurs in living individuals, thereby linking genes directly to real-time brain function."

Implications

The study demonstrated that this transcriptional program is reproducible across independent groups and aligns with established pathways involved in excitatory neuronal signaling and synaptic function. These findings establish a molecular framework for understanding how gene activity supports active brain communication.

Dr. Brian Kopell, Director of the Center for Neuromodulation, highlighted the importance of integrating electrophysiology and molecular science.

"This approach bridges two fields traditionally studied separately, providing a clearer understanding of how neural circuits operate at both electrical and genetic levels."

Disrupted neurotransmission is a factor in many psychiatric and neurological disorders, including depression, schizophrenia, epilepsy, and neurodegenerative diseases. Identifying the genes linked to active signaling could help refine future diagnostic tools and therapeutic strategies.

Dr. Ignacio Saez, Associate Professor at the Icahn School of Medicine, added that the study's integration of large-scale transcriptomic data with direct measures of brain activity offers a new framework for understanding how genetic variation may influence brain function and vulnerability to disease.

"This integration of large-scale transcriptomic data with direct measures of brain activity offers a new framework for understanding how genetic variation may influence brain function and vulnerability to disease."