Absence of Serotonin Alters Development and Function of Brain Circuits

Researchers at Case Western Reserve University School of Medicine have created the first complete model to describe the role that serotonin plays in brain development and structure. Serotonin, also called 5-hydroxytryptamine [5-HT], is an important neuromodulator of brain development and the structure and function of neuronal (nerve cell) circuits. The results were published in the current issue of The Journal of Neurophysiology online.

“Our goal in the project was to close the gap in knowledge that exists on role of serotonin in the brain cortex, particularly as it concerns brain circuitry, its electrical activity and function,” said Roberto Fernández Galán, PhD, Assistant Professor in the Department of Neurosciences at Case Western Reserve University School of Medicine. “For the first time, we can provide a complete description of an animal model from genes to behavior—including at the level of neuronal network activity, which has been ignored in most studies to date.”

Dr. Galán and his team used high-density multi-electrode arrays in a mouse model of serotonin deficiency to record and analyze neuronal activity. The study supports the importance of the serotonin which is specified and maintained by a specific gene, the Pet-1 gene – for normal functioning of the neurons, synapses and networks in the cortex, as well as proper development of brain circuitry. Serotonin abnormalities have been linked to autism and epilepsy, depression and anxiety. By more fully elucidating the role of serotonin in the brain, this study may contribute to a better understanding of the development or treatment of these conditions.

“By looking at the circuit level of the brain, we now have new insight into how the brain becomes wired and sensitive to changing serotonin levels.” added Dr. Galán.

In addition to Dr. Galán, who served as senior author of the study, former graduate student, Pavel A. Puzerey, and undergraduate student majoring in Physics, Nathan X. Kodama, contributed to this project. Dr. Galán’s research is funded with a Biomedical Researcher Award from The Hartwell Foundation.

Visit: www.case.edu/medicine.

Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.

Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's "Guide to Graduate Education."

The School of Medicine is affiliated with University Hospitals Cleveland Medical Center, MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. case.edu/medicine.

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