Summary: Columbia University researchers reveal targeting a specific serotonin receptor can help to boost memory formation. The study reports targeting 5-HT4 receptors could help improve cognitive impairment.
Source: Columbia University.
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.
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).
Funding: 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.).
Source: Eian Kantor – Columbia University
Publisher: Organized by NeuroscienceNews.com.
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Original Research: Abstract for “Hippocampal 5-HT Input Regulates Memory Formation and Schaffer Collateral Excitation” by Catia M. Teixeira, Zev B. Rosen, Deepika Suri, Qian Sun, Marc Hersh, Derya Sargin, Iva Dincheva, Ashlea A. Morgan, Stephen Spivack, Anne C. Krok, Tessa Hirschfeld-Stoler, Evelyn K. Lambe, Steven A. Siegelbaum, Mark S. Ansorge in Neuron. Published May 10 2018.
Hippocampal 5-HT Input Regulates Memory Formation and Schaffer Collateral Excitation
•Evoked terminal release of serotonin in CA1 potentiates CA3-to-CA1 inputs
•5-HT4 receptors mediate the potentiation of CA3-to-CA1 inputs
•Optogenetic stimulation of serotonergic axons in CA1 increases spatial memory
•Optogenetic inhibition of serotonergic axons in CA1 impairs spatial memory
The efficacy and duration of memory storage is regulated by neuromodulatory transmitter actions. While the modulatory transmitter serotonin (5-HT) plays an important role in implicit forms of memory in the invertebrate Aplysia, its function in explicit memory mediated by the mammalian hippocampus is less clear. Specifically, the consequences elicited by the spatio-temporal gradient of endogenous 5-HT release are not known. Here we applied optogenetic techniques in mice to gain insight into this fundamental biological process. We find that activation of serotonergic terminals in the hippocampal CA1 region both potentiates excitatory transmission at CA3-to-CA1 synapses and enhances spatial memory. Conversely, optogenetic silencing of CA1 5-HT terminals inhibits spatial memory. We furthermore find that synaptic potentiation is mediated by 5-HT4 receptors and that systemic modulation of 5-HT4 receptor function can bidirectionally impact memory formation. Collectively, these data reveal powerful modulatory influence of serotonergic synaptic input on hippocampal function and memory formation.