Dopaminergic neurons inhibit striatal output via non-canonical release of GABA

DSpace/Manakin Repository

Dopaminergic neurons inhibit striatal output via non-canonical release of GABA

Citable link to this page

 

 
Title: Dopaminergic neurons inhibit striatal output via non-canonical release of GABA
Author: Tritsch, Nicolas X.; Ding, Jun B.; Sabatini, Bernardo L.

Note: Order does not necessarily reflect citation order of authors.

Citation: Tritsch, Nicolas X., Jun B. Ding, and Bernardo L. Sabatini. 2012. “Dopaminergic neurons inhibit striatal output via non-canonical release of GABA.” Nature 490 (7419): 262-266. doi:10.1038/nature11466. http://dx.doi.org/10.1038/nature11466.
Full Text & Related Files:
Abstract: The substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) contain the two largest populations of dopamine (DA)-releasing neurons in the mammalian brain. These neurons extend elaborate projections in striatum, a large subcortical structure implicated in motor planning and reward-based learning. Phasic activation of dopaminergic neurons in response to salient or reward-predicting stimuli is thought to modulate striatal output via the release of DA to promote and reinforce motor action1–4. Here we show that activation of DA neurons in striatal slices rapidly inhibits action potential firing in both direct-and indirect-pathway striatal projection neurons (SPNs) through vesicular release of the inhibitory transmitter γ-aminobutyric acid (GABA). GABA is released directly from dopaminergic axons but in a manner that is independent of the vesicular GABA transporter VGAT. Instead GABA release requires activity of the vesicular monoamine transporter VMAT2, which is the vesicular transporter for DA. Furthermore, VMAT2 expression in GABAergic neurons lacking VGAT is sufficient to sustain GABA release. Thus, these findings expand the repertoire of synaptic mechanisms employed by DA neurons to influence basal ganglia circuits, reveal a novel substrate whose transport is dependent on VMAT2, and demonstrate that GABA can function as a bona fide co-transmitter in monoaminergic neurons.
Published Version: doi:10.1038/nature11466
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944587/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12064437
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters