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.
- 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.
- 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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