Researchers have identified a distinct gene expression program associated with neurotransmission in the living human brain, according to findings published on Feb. 19 in Molecular Psychiatry.
The study is significant because it provides new insight into the molecular mechanisms that support cognition, emotion, and behavior. Previously, most research on gene expression in the human brain relied on postmortem tissue, which limited understanding of genes involved in real-time neuronal communication.
In this research, scientists combined gene expression profiling from the prefrontal cortex with direct intracranial measures of neurotransmission collected from more than 100 individuals undergoing neurosurgical procedures. This approach allowed them to identify a coordinated set of genes whose activity aligns with neuronal signaling—a transcriptional program associated with neurotransmission.
Alexander Charney, MD, PhD, Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, said: "For decades, our understanding of gene expression in the human brain has been limited to postmortem studies. This work allows us to examine the molecular architecture of neurotransmission as it is happening in living individuals, bringing us closer to directly linking genes to real-time brain function."
The study found that this transcriptional program is reproducible across independent groups and matches established pathways involved in excitatory neuronal signaling and synaptic function. Brian Kopell, MD, Director of the Center for Neuromodulation and Co-Director of The Mount Sinai Hospital's Movement Disorders Program said: "By pairing intracranial recordings with molecular profiling, we're bridging two worlds that have traditionally been studied separately. This approach gives us a clearer picture of how neural circuits operate at both the electrical and genetic levels, which has profound implications for neuromodulation and precision treatments."
Because disrupted neurotransmission plays a role in many psychiatric and neurological disorders such as depression, schizophrenia, epilepsy, and neurodegenerative diseases, identifying genes linked to active signaling could help improve future diagnostic tools and therapies. Ignacio Saez, PhD, Associate Professor of Neuroscience, Neurosurgery, and Neurology at Icahn School of Medicine at Mount Sinai said: "The power of this study lies in its integration of large-scale transcriptomic data with direct measures of brain activity. Identifying a coordinated transcriptional program associated with neurotransmission provides a new framework for understanding how genetic variation may influence brain function and vulnerability to disease."
