New York, NY (May 10, 2018)–In a breakthrough that could one day help individuals with cognitive impairment, researchers at Columbia University Irving Medical Center (CUIMC) identified a specific receptor related to the neurotransmitter serotonin that could be targeted with drugs to boost memory.
The researchers, who examined the role of serotonin in the hippocampus of mice, published their findings online today in the journal Neuron.
"First, we found that when serotonin is released from its endogenous pools within the hippocampus during learning, memory of the learned event is strengthened. We then reasoned that by identifying a dominant involvement for one type of serotonin receptor, we could test drug treatments on memory performance. Indeed, we found that systemic modulation of 5-HT4 receptor function with drugs enhanced memory formation," said Catia M Teixeira, PhD, a Research Scientist at CUIMC, who co-led the study along with Zev B Rosen, PhD, a neuroscientist at Massachusetts Institute of Technology who was previously at Columbia University's Kavli Institute for Brain Science.
The hippocampus region of the brain is essential for forming new memories about experienced events. The strength of neuronal communication–the method by which messages pass within the brain–in the CA1 region of the hippocampus provides a basis for memory. While the hippocampus receives strong serotonin input, if and how these serotonin pathways influence neural circuits and memory formation has largely been unknown.
The researchers used optogenetics–which uses light to stimulate or inhibit activity in neurons–to learn how a specific serotonin pathway that targets the CA1 region of the hippocampus influences neuronal communication, memory formation, and behavior in the mice. They found that when more serotonin was released, neuronal communication in CA1 strengthened and the animals' spatial memory improved. When the pathway was blocked, spatial memory was impaired, demonstrating that serotonin release in CA1 is not only sufficient to boost memory formation, but also necessary for normal memory formation.
"Our data reveal the powerful modulatory influence of serotonin on hippocampal function and memory formation, and they support the rationale to target 5-HT4 receptors for pharmacotherapy of cognitive impairment," said Dr. Ansorge, the senior author of the study.
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The study is titled, "Hippocampal 5-HT input regulates memory formation and Schaffer collateral excitation."
This work has been supported by the National Institute of Mental Health (1R01MH113569 – 01, M.S.A), and the Sackler Institute for Developmental Psychobiology (M.S.A.).
The other contributors to this paper are Deepika Suri, PhD (CUIMC), Qian Sun, PhD (CUIMC/Kavli Institute), Marc Hersh (CUIMC), Derya Sargin, PhD (University of Toronto), Iva Dincheva, PhD (CUIMC/NYSPI), Ashlea A. Morgan (CUIMC), Stephen Spivack (CUIMC), Anne C. Krok (CUIMC/NYSPI), Tessa Hirschfeld-Stoler (CUIMC), Evelyn K Lambe, PhD (University of Toronto), Steven A Siegelbaum, PhD (CUIMC/Kavli Institute), and Mark S Ansorge, PhD (CUIMC/NYSPI).
Columbia University Department of Psychiatry
Columbia Psychiatry is among the top ranked psychiatry departments in the nation and has contributed greatly to the understanding and treatment of brain disorders. Co-located at the New York State Psychiatric Institute on the NewYork-Presbyterian Hospital/Columbia University Irving Medical Center campus in Washington Heights, the department enjoys a rich and productive collaborative relationship with physicians in various disciplines at the Columbia University Vagelos College of Physicians and Surgeons. Columbia Psychiatry is home to distinguished clinicians and researchers noted for their clinical and research advances in the diagnosis and treatment of depression, suicide, schizophrenia, bipolar and anxiety disorders, eating disorders, substance use disorders, and childhood psychiatric disorders.
Columbia University Irving Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the Vagelos College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Irving Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.
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