Integrative Neuroscience Research Branch - The Intramural Research Program of the National Institute on Drug Abuse

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Integrative Neuroscience RESEARCH BRANCH

Branch Overview

Branch Chief: Marisela Morales, Ph.D. on-site page link

The Integrative Neuroscience Branch conducts research at the cellular, molecular, and systems levels to identify the neural substrates upon which drugs of abuse act to produce long-term alterations in behavior and brain function. The aims of our research are to:

  • Delineate the afferent inputs, efferent targets, physiological characteristics, and behavioral functions of ventral tegmental area and dorsal raphe neurons. In order to accomplish this, we utilize classical tract tracing techniques, radioactive and nonradioactive in situ hybridization, ex vivo electrophysiological recordings, in vivo single-unit electrophysiological recordings, optogenetics, pharmacogenetics, and behavioral assays (Neuronal Networks Section);
  • Identify drug-evoked alterations in sigma receptor function and interorganellar signaling between the endoplasmic reticulum, mitochondrion, and nucleus that lead to abnormalities in neuronal function and structure associated with the chronic use of abused drugs (Cellular Pathobiology Section)
  • Studies the role of endoplasmic reticulum stress and inflammation in neuronal dysfunction caused by substance abuse or neurodegenerative diseases (Molecular Mechanisms of Cellular Stress and Inflammation)

Neuronal Networks Section - click for larger versionNeuronal Networks Section - click for larger version

Neuronal Networks Section

Section Chief: Marisela Morales, Ph.D. on-site page link

Investigation of molecules, cells and neuronal pathways central to the neurobiology of addiction. Application of anatomical, molecular, cell biological and electrophysiological approaches to investigate:

  • Interactions between the stress and reward systems
  • Cellular composition and neuronal connectivity of the ventral tegmental area

Cellular Pathobiology Section - click for larger version

Cellular Pathobiology Section - click for larger version

Cellular Pathobiology Section

Section Chief: Tsung-Ping Su, Ph.D. on-site page link
  • Studies of cellular biological processes underlying addiction and related pathobiological disorders
  • Examination of signaling processes through which drugs of abuse alter neuronal structure and function
  • Biological and biochemical characterization of sigma receptors

Behavioral Neuroscience Section

Section Chief: Roy Wise, Ph.D. on-site page link

Projects include:

  • Characterization of brain circuitry associated with drug reward and reward prediction. Current studies focus on the mesolimbic and nigrostriatal dopamine systems and their glutamatergic and cholinergic inputs.
  • Neuroadaptations in reward circuitry resulting from drug experience and stress. Current interest is in changes in CRF and glutamate signaling that is altered in cocaine-experienced rats.
  • Comparative microdialysis studies of the acquisition, extinction, and reinstatement of cocaine-seeking, heroin-seeking and other drug-seeking habits.

Structural Biology Unit - click for larger version

Structural Biology Unit - click for larger version

Neurobiology of Addiction Section

Section Chief: George F. Koob, Ph.D. on-site page link
  • Conduct research towards understanding the neurobiological bases for altered motivational states associated with drug addiction at the neurocircuitry, cellular and molecular level and using these studies as a heuristic approach to the study of emotions.
  • Conduct research on the relationship between pain and emotional systems in the context of the same neurocircuitry. The neurocircuitry under study involves specific elements of the basal forebrain involving the elements of the extended amygdala: central nucleus of the amygdala, bed nucleus of the stria terminalis and elements of the ventral striatum including the shell and core of the nucleus accumbens.
  • Conduct research on the identification of molecular factors that load such circuits and neurotransmitter system function, on identification of cellular interactions between such brain stress systems, and on identification of the role of outputs such as the hypothalamus in expressing such negative emotional states. Such research will provide key information not only about the neurobiology of addiction, pain and stress but also key information about the neurobiology of motivational systems in general.
  • The ultimate goal of the section is to understand how cellular and molecular changes produce changes in particular neurocircuits to convey negative emotional states that contribute to the motivation to seek drugs.

Lab Page

Molecular Mechanisms of Cellular Stress and Inflammation

Section Chief: Brandon Harvey, Ph.D. on-site page link
  • Studies the role of endoplasmic reticulum stress and inflammation in neuronal dysfunction caused by substance abuse or neurodegenerative diseases
  • Identified and studies the biology of secreted ER calcium modulated proteins (SERCaMPs) and KDEL receptors
  • Examining the influence of drugs of abuse and SERCaMPs on microglial activation
  • Develops genetic and pharmacological tools to monitor and modulate ER calcium

Related Information...

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The National Institute on Drug Abuse (NIDA), is part of the National Institutes of Health (NIH), the principal biomedical and behavioral research agency of the United States Government. NIH is a component of the U.S. Department of Health and Human Services.

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