Abstract

The synapse is altered by learning and by prolonged exposure to psychoactive drugs.Release of neurotransmitter at the synapse depends on the rates at which synaptic vesicles fuse with the plasma membrane, then recycle and refill. Recently, proteins involved in the fusion step have been identified and shown to form a fusion complex of vesicle and plasma membrane proteins. In addition, an assay has been developed in this lab that screens for the proteins involved in vesicle recycling. The other two proposals also address vesicle refilling. There is evidence that one or more of these three steps in the synaptic cycle are modified by psychoactive drugs. in this proposal assays of fusion complexes and of synaptic vesicle biogenesis will be developed using the neuroendocrine, dopamine-secreting cell line, PC12, since dopamine pathways appear to be central to drug abuse. To determine how the molecules involved in these two steps of the synaptic vesicle cycle are regulated by short-term and long-term modifications, the assays will be used to detect changes in response to secretagogues, NGF, synaptic modulators and selected psychoactive substances.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Program Projects (P01)
Project #
5P01DA010154-04
Application #
6104146
Study Section
Project Start
1998-09-30
Project End
1999-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Henke, Adam; Kovalyova, Yekaterina; Dunn, Matthew et al. (2018) Toward Serotonin Fluorescent False Neurotransmitters: Development of Fluorescent Dual Serotonin and Vesicular Monoamine Transporter Substrates for Visualizing Serotonin Neurons. ACS Chem Neurosci 9:925-934
Dunn, Matthew; Boltaev, Umed; Beskow, Anne et al. (2018) Identification of Fluorescent Small Molecule Compounds for Synaptic Labeling by Image-Based, High-Content Screening. ACS Chem Neurosci 9:673-683
Borgkvist, Anders; Lieberman, Ori J; Sulzer, David (2018) Synaptic plasticity may underlie l-DOPA induced dyskinesia. Curr Opin Neurobiol 48:71-78
Liang, Samantha I; van Lengerich, Bettina; Eichel, Kelsie et al. (2018) Phosphorylated EGFR Dimers Are Not Sufficient to Activate Ras. Cell Rep 22:2593-2600
Clark, Samuel D; Mikofsky, Rachel; Lawson, Jacqueline et al. (2018) Piezo High Accuracy Surgical Osteal Removal (PHASOR): A Technique for Improved Cranial Window Surgery in Mice. J Vis Exp :
Siljee, Jacqueline E; Wang, Yi; Bernard, Adelaide A et al. (2018) Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity. Nat Genet 50:180-185
Eichel, Kelsie; Jullié, Damien; Barsi-Rhyne, Benjamin et al. (2018) Catalytic activation of ?-arrestin by GPCRs. Nature 557:381-386
Dunn, Matthew; Henke, Adam; Clark, Samuel et al. (2018) Designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo. Nat Commun 9:2838
Fischer, Kathryn D; Houston, Alex C W; Desai, Rajeev I et al. (2018) Behavioral phenotyping and dopamine dynamics in mice with conditional deletion of the glutamate transporter GLT-1 in neurons: resistance to the acute locomotor effects of amphetamine. Psychopharmacology (Berl) 235:1371-1387
Eichel, Kelsie; von Zastrow, Mark (2018) Subcellular Organization of GPCR Signaling. Trends Pharmacol Sci 39:200-208

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