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.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Neurobiology of Motivated Behavior Study Section (NMB)
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Volman, Susan
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Children's Hospital Boston
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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
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
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
Bang, Sun Jung; Jensen, Patricia; Dymecki, Susan M et al. (2012) Projections and interconnections of genetically defined serotonin neurons in mice. Eur J Neurosci 35:85-96
Soiza-Reilly, Mariano; Commons, Kathryn G (2011) Glutamatergic drive of the dorsal raphe nucleus. J Chem Neuroanat 41:247-55
Bang, S J; Commons, K G (2011) Age-dependent effects of initial exposure to nicotine on serotonin neurons. Neuroscience 179:1-8
Soiza-Reilly, Mariano; Commons, Kathryn G (2011) Quantitative analysis of glutamatergic innervation of the mouse dorsal raphe nucleus using array tomography. J Comp Neurol 519:3802-14
Sperling, Robin; Commons, Kathryn G (2011) Shifting topographic activation and 5-HT1A receptor-mediated inhibition of dorsal raphe serotonin neurons produced by nicotine exposure and withdrawal. Eur J Neurosci 33:1866-75
Bajic, D; Commons, K G (2010) Acute noxious stimulation modifies morphine effect in serotonergic but not dopaminergic midbrain areas. Neuroscience 166:720-9
Commons, K G (2010) Neuronal pathways linking substance P to drug addiction and stress. Brain Res 1314:175-82

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