Opioid Control of Identified Midbrain GABAergic Synapses

Information

  • Research Project
  • 8266365
  • ApplicationId
    8266365
  • Core Project Number
    R01DA029776
  • Full Project Number
    5R01DA029776-02
  • Serial Number
    029776
  • FOA Number
    PA-07-070
  • Sub Project Id
  • Project Start Date
    6/1/2011 - 13 years ago
  • Project End Date
    3/31/2016 - 8 years ago
  • Program Officer Name
    SORENSEN, ROGER
  • Budget Start Date
    4/1/2012 - 12 years ago
  • Budget End Date
    3/31/2013 - 11 years ago
  • Fiscal Year
    2012
  • Support Year
    02
  • Suffix
  • Award Notice Date
    3/16/2012 - 12 years ago

Opioid Control of Identified Midbrain GABAergic Synapses

DESCRIPTION (provided by applicant): Dopamine (DA) neurons in the midbrain ventral tegmental area (VTA) play an important role in the rewarding and reinforcing effects of opioids. Within the VTA, opioids acting at the mu opioid receptor inhibit the release of GABA, which leads to the disinhibition of DA neurons (Johnson and North, 1992a). However, GABA synapses onto VTA DA neurons arise not only from local GABAergic neurons, but also from extrinsic sources, at least some of which are likely to be sensitive to opioids. Two major external sources of inhibition onto VTA neurons arise from the nucleus accumbens (NAc) and the ventral pallidum (VP), both of which have been strongly implicated in opioid reward. These inputs have not been well defined, largely due to the technical challenge of isolating individual connections. Nevertheless, our understanding of the neural circuitry underlying opioid reward requires a thorough investigation of the synaptic properties of these VTA afferents. In this grant, we will make use of recently developed optogenetic tools to independently activate axon terminals arising from either the NAc or the VP in conjunction with whole cell patch-clamp electrophysiology from VTA neurons in midbrain slices. This will allow us to compare and contrast these two inputs and to determine how they are regulated by both acute and chronic exposure to opioids. In addition, by combining this powerful technique with retrograde labeling of VTA neurons from particular projection targets, we will be able to determine the detailed microcircuitry of these afferents within the VTA. The data provided by these studies will provide critical information for the development of circuit based models of limbic system function.

IC Name
NATIONAL INSTITUTE ON DRUG ABUSE
  • Activity
    R01
  • Administering IC
    DA
  • Application Type
    5
  • Direct Cost Amount
    225000
  • Indirect Cost Amount
    150300
  • Total Cost
    375300
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    279
  • Ed Inst. Type
  • Funding ICs
    NIDA:375300\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    NMB
  • Study Section Name
    Neurobiology of Motivated Behavior Study Section
  • Organization Name
    ERNEST GALLO CLINIC AND RESEARCH CENTER
  • Organization Department
  • Organization DUNS
    173995366
  • Organization City
    EMERYVILLE
  • Organization State
    CA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    946082007
  • Organization District
    UNITED STATES