It remains poorly understood how serotonin circuits in the brain dysfunction in depression, drug addiction and other disorders. Understanding the role of serotonin neurotransmission in psychopathology is complicated by one of the most salient features of the serotonin system: it?s neuroanatomy. In this project we examine how serotonin neuron function changes in animal models of depression and nicotine abstinence, and after antidepressant treatment. Our work seeks to reconcile behavioral pharmacology with neuroanatomy to resolve some of the contradictory findings in the field. The over-riding hypothesis is that there are topographically organized changes in the activation of serotonin neurons in depression and these are resolved by antidepressant treatment. In addition, we examine how feedback inhibition mediated by 5-HT1A receptors changes in coordination with altered patterns of serotonin-neuron activity. Finally we examine the functional impact of topographically selective changes in activation state on behavior.
The specific aims i ntegrate cellular, systems and behavioral approaches to understand function and dysfunction of serotonin neurotransmission. The broad long-term goal of this research program is to provide a better understanding of the role of serotonin in affective and addictive disorders.

Public Health Relevance

The proposed studies will help understand how serotonin networks dysfunction in depression and drug addiction, and will further our understanding of exactly how antidepressants work to correct disorders of serotonin neurotransmission. The results will increase the knowledge base supporting improved treatment strategies for mood- and addictive-disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA021801-06A1
Application #
8629145
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Volman, Susan
Project Start
2006-07-01
Project End
2019-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
6
Fiscal Year
2014
Total Cost
$360,117
Indirect Cost
$155,117
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Commons, Kathryn G (2016) Ascending serotonin neuron diversity under two umbrellas. Brain Struct Funct 221:3347-60
Commons, Kathryn G (2015) Two major network domains in the dorsal raphe nucleus. J Comp Neurol 523:1488-504
Soiza-Reilly, Mariano; Goodfellow, Nathalie M; Lambe, Evelyn K et al. (2015) Enhanced 5-HT1A receptor-dependent feedback control over dorsal raphe serotonin neurons in the SERT knockout mouse. Neuropharmacology 89:185-92
Bajic, Dusica; Soiza-Reilly, Mariano; Spalding, Allegra L et al. (2015) Endogenous cholinergic neurotransmission contributes to behavioral sensitization to morphine. PLoS One 10:e0117601
Soiza-Reilly, Mariano; Commons, Kathryn G (2014) Unraveling the architecture of the dorsal raphe synaptic neuropil using high-resolution neuroanatomy. Front Neural Circuits 8:105
Corcoran, Andrea E; Commons, Kathryn G; Wu, Yuanming et al. (2014) Dual effects of 5-HT(1a) receptor activation on breathing in neonatal mice. J Neurosci 34:51-9
Soiza-Reilly, Mariano; Anderson, Wayne B; Vaughan, Christopher W et al. (2013) Presynaptic gating of excitation in the dorsal raphe nucleus by GABA. Proc Natl Acad Sci U S A 110:15800-5
Bajic, Dusica; Commons, Kathryn G; Soriano, Sulpicio G (2013) Morphine-enhanced apoptosis in selective brain regions of neonatal rats. Int J Dev Neurosci 31:258-66
Massey, Caitlin A; Kim, Gloria; Corcoran, Andrea E et al. (2013) Development of brainstem 5-HT1A receptor-binding sites in serotonin-deficient mice. J Neurochem 126:749-57
Templin, J Scott; Bang, Sun Jung; Soiza-Reilly, Mariano et al. (2012) Patterned expression of ion channel genes in mouse dorsal raphe nucleus determined with the Allen Mouse Brain Atlas. Brain Res 1457:1-12

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