Corelease of dopamine and GABA by a retinal dopaminergic neuron

Hajime Hirasawa, Rebecca Betensky, Elio Raviola

Research output: Contribution to journalArticle

Abstract

Numerous neurons release two transmitters of low molecular mass, but it is controversial whether they are localized within the same synaptic vesicle, with the single exception of GABA and glycine because they are ferried into the vesicle by the same transporter. Retinal dopaminergic (DAergic) amacrine cells synthesize both dopamine (DA) and GABA. Both transmitters are released over the entire cell surface and act on neighboring and distant neurons by volume transmission, but, in addition, DAergic cells establish GABAergic synapses onto AII amacrine cells, the neurons that transfer rod signals to cone bipolars. By combining recordings of DA and GABA release from isolated, genetically identified perikarya of DAergic cells from the mouse retina, we observed that a proportion of the events of DA and GABA exocytosis were simultaneous, suggesting corelease. Furthermore, a proportion of the secretory organelles in the perikaryon and synaptic endings of DAergic cells contained both vesicular transporters for DA [vesicular monoamine transporter 2 (VMAT2)] and GABA [vesicular GABA transporter (VGAT)]. Because the majority of the DA release events concerned a single transmitter and organelles were present that contained a single transporter, either VMAT2 or VGAT, we conclude that the secretory organelles of DAergic cells contain variable concentrations of the two transmitters, which are in turn determined by a variable mixture of the two transporter molecules in their limiting membrane. This variability can be explained if the relative numbers of transporter molecules is determined stochastically during the budding of the somatic organelles from the trans-Golgi network or the retrieval of the vesicular membrane from the plasmalemma after exocytosis.

Original languageEnglish (US)
Pages (from-to)13281-13291
Number of pages11
JournalJournal of Neuroscience
Volume32
Issue number38
DOIs
StatePublished - Sep 19 2012

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Retinal Neurons
Dopaminergic Neurons
gamma-Aminobutyric Acid
Dopamine
Organelles
Vesicular Monoamine Transport Proteins
Amacrine Cells
Exocytosis
Neurons
trans-Golgi Network
Dopamine Plasma Membrane Transport Proteins
Membranes
Synaptic Vesicles
Synapses
Glycine
Retina

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Corelease of dopamine and GABA by a retinal dopaminergic neuron. / Hirasawa, Hajime; Betensky, Rebecca; Raviola, Elio.

In: Journal of Neuroscience, Vol. 32, No. 38, 19.09.2012, p. 13281-13291.

Research output: Contribution to journalArticle

Hirasawa, Hajime ; Betensky, Rebecca ; Raviola, Elio. / Corelease of dopamine and GABA by a retinal dopaminergic neuron. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 38. pp. 13281-13291.
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