title: Synaptic vesicle transporter expression regulates vesicle phenotype and quantal size.
abstract: While the transporters that accumulate classical neurotransmitters in synaptic vesicles have been identified, little is known about how their expression regulates synaptic transmission. We have used adenoviral-mediated transfection to increase expression of the brain vesicular monoamine transporter VMAT2 and presynaptic amperometric recordings to characterize the effects on quantal release. In presynaptic axonal varicosities of ventral midbrain neurons in postnatal culture, VMAT2 overexpression in small synaptic vesicles increased both quantal size and frequency, consistent with the recruitment of synaptic vesicles that do not normally release dopamine. This was confirmed using noncatecholaminergic AtT-20 cells, in which VMAT2 expression induced the quantal release of dopamine. The ability to increase quantal size in vesicles that were already competent for dopamine release was shown in PC12 cells, in which VMAT2 expression increased the quantal size but not the number of release events. These results demonstrate that vesicle transporters limit the rate of transmitter accumulation and can alter synaptic strength through two distinct mechanisms.
authors.affiliation: Departments of Neurology and Psychiatry, Columbia University, New York, New York 10032, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Pothos
authors.forename: K E
authors.initials: KE
authors.lastname: Larsen
authors.forename: D E
authors.initials: DE
authors.lastname: Krantz
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: J W
authors.initials: JW
authors.lastname: Haycock
authors.forename: W
authors.initials: W
authors.lastname: Setlik
authors.forename: M D
authors.initials: MD
authors.lastname: Gershon
authors.forename: R H
authors.initials: RH
authors.lastname: Edwards
authors.forename: D
authors.initials: D
authors.lastname: Sulzer
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001369:Axons / Q000378:metabolism; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D004563:Electrochemistry; D005089:Exocytosis; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D026901:Membrane Transport Proteins; D051379:Mice; D008839:Microelectrodes; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides; D010641:Phenotype; D016012:Poisson Distribution; D017729:Presynaptic Terminals / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism*; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
chemical_list: D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; C493453:Slc18a2 protein, mouse; C493454:Slc18a2 protein, rat; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine