Role of serotonin signaling in limbic system development
Neuronal activity during development critically shapes the functional connectivity between neurons, and thus influences the “wiring diagram” of the brain. Best characterized in the development of sensory systems, such plasticity is often restricted to developmental time windows, referred to as sensitive periods. My lab studies sensitive periods that impact the formation of neuronal circuits underlying emotional behavior and cognition.
We have identified two sensitive developmental periods during which the strength of monoaminergic signaling affects adult behavior: (1) an early postnatal serotonin-sensitive period that impacts cognition, anxiety and depression-related behaviors, and (2) a later peri-adolescent dopamine- and serotonin-sensitive period affecting aggression, impulsivity and behavioral response to amphetamine. Our findings indicate that neuropsychiatric disorders characterized by alterations in these behavioral domains may have developmental origins. Thus, genetic, epigenetic and environmental factors that impact serotonin and/or dopamine signaling during specific periods of development might impact the risk for depression, anxiety disorders, schizophrenia and substance abuse.
Which neural circuits are sensitive to monoaminergic signaling during restricted developmental periods? What functional circuit parameters are affected? How do changes in circuit function relate to behavior? These questions currently guide most projects in the lab. Beginning to address them, we have identified period-specific molecular, anatomical, physiological, and circuitry-related correlates in the raphe, ventral tegmental area, hippocampus, and medial prefrontal cortex—brain regions involved in emotional and cognitive processing and regulation. Consequently, we hypothesize that altered function of these regions and circuitry involving them gives rise to the observed behavioral changes. To test for such causal relationships, we apply pharmacological, genetic, pharmacogenetic, and optogenetic approaches.
- Elena Y Demireva, Deepika Suri, Emanuela Morelli, Darshini Mahadevia, Nao Chuhma, Catia M Teixeira, Annette Ziolkowski, Marc Hersh, James Fifer, Sneha Bagchi, Alexei Chemiakine, Holly Moore, Jay A Gingrich, Peter Balsam, Stephen Rayport, Mark S Ansorge. 5-HT2C receptor blockade reverses SSRI-associated basal ganglia dysfunction and potentiates therapeutic efficacy. Mol Psychiatry. 2018 Aug 17.
- 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 SA, Mark S Ansorge. Hippocampal 5-HT Input Regulates Memory Formation and Schaffer Collateral Excitation. Neuron. 2018 May 10.
- Anne Teissier, Alexei Chemiakine, Benjamin Inbar, Sneha Bagchi, Russell R Ray, Richard D Palmiter, Susan M Dymecki, Holly Moore, Mark S Ansorge. Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors. Cell Rep. 2015 Dec 1;13(9):1965-76.
- Tahilia J. Rebello, Qinghui Yu, Nathalie M. Goodfellow, Martha Caffrey Cagliostro, Anne Teissier, Emanuela Morelli, Elena Y. Demireva, Alexei Chemiakine, Gorazd B. Rosoklija, Andrew J. Dwork, Evelyn K. Lambe, Jay A. Gingrich and Mark S. Ansorge. Postnatal day 2 to 11 constitutes a 5-HT sensitive period impacting adult mPFC function. J Neurosci. 2014 Sep 10;34(37):12379-93.
- Deepika Suri, Cátia M. Teixeira, Martha K. Caffrey Cagliostro, Darshini Mahadevia, Mark S. Ansorge. Monoamine-sensitive developmental periods impacting adult emotional and cognitive behaviors. Neuropsychopharmacology 2015 Jan;40(1):88-112.
- 2018 – 2023 Serotonin and the Modulation of Brain Development: Study of the mechanisms underlying the impact of early SSRI exposure on adult emotional function in mice (Gingrich). NIMH (2R01MH080116-06A1), Co-I
- 2017 – 2022 Serotonergic modulation of hippocampal function (Ansorge), NIMH (R01 MH099118-01A1), PI
- 2017 – 2020 Defining the Role of the 5-HT4 Receptor in the Brain, Behavior, and Gut Abnormalities Resulting from In Utero SSRI Exposure (Gross-Margolis, Ansorge), DoD (PR160365P1), Co-PI
- NIMH (1 P50 MH90966-01) (Gingrich)
07/01/10 to 06/30/15
Serotonergic Modulation of Brain Development: Genetic and Pharmacologic Influences on Structure, Function, and Behavior.
Projects 1 – 3 of this Conte Center study the consequences of developmentally perturbed serotonin signaling on human brain development and behavior. Project 4 investigates serotonin-mediated genetic and pharmacologic influences on the development of brain structure and behavior of rodents and primates.
Role on Project: Co-Investigator, Co-PI Project 4
- NIMH (1R01MH099118-01) (Ansorge)
03/01/13 to 02/28/18
Developmental Origins of Aggressive and Impulsive Behavior.
This study examines the effects of early-life 5-HTT and DAT blockade on the development of DA function and behavior.
NARSAD Young Investigator Award (Teissier)
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