VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons

The ventral tegmental area (VTA) is best known for its dopamine neurons, some of which project to nucleus accumbens (nAcc). However, the VTA also has glutamatergic neurons that project to nAcc. The function of the mesoaccumbens-glutamatergic pathway remains unknown. Here, we report that nAcc photoac...

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Main Authors:	Qi, Jia, Zhang, Shiliang, Wang, Hui-Ling, Barker, David J., Miranda-Barrientos, Jorge, Morales, Marisela
Format:	Online
Language:	English
Published:	2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846550/

id	pubmed-4846550
recordtype	oai_dc
spelling	pubmed-48465502016-09-28 VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons Qi, Jia Zhang, Shiliang Wang, Hui-Ling Barker, David J. Miranda-Barrientos, Jorge Morales, Marisela Article The ventral tegmental area (VTA) is best known for its dopamine neurons, some of which project to nucleus accumbens (nAcc). However, the VTA also has glutamatergic neurons that project to nAcc. The function of the mesoaccumbens-glutamatergic pathway remains unknown. Here, we report that nAcc photoactivation of mesoaccumbens-glutamatergic fibers promotes aversion. Although we found that these mesoaccumbens-glutamate-fibers lack GABA, the aversion evoked by their photoactivation depends on glutamate and GABA receptor signaling, and not on dopamine receptor signaling. We found that mesoaccumbens-glutamatergic-fibers establish multiple asymmetric synapses on single parvalbumin-GABAergic interneurons, and that nAcc photoactivation of these fibers drives AMPA-mediated cellular firing of parvalbumin-GABAergic interneurons. These parvalbumin-GABAergic-interneurons, in turn, inhibit nAcc medium spiny output neurons, as such, controlling inhibitory neurotransmission within nAcc. The mesoaccumbens-glutamatergic pathway is the first glutamatergic input to nAcc shown to mediate aversion, instead of reward, and the first pathway shown to establish excitatory synapses on nAcc parvalbumin-GABAergic interneurons. 2016-03-28 2016-05 /pmc/articles/PMC4846550/ /pubmed/27019014 http://dx.doi.org/10.1038/nn.4281 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Qi, Jia Zhang, Shiliang Wang, Hui-Ling Barker, David J. Miranda-Barrientos, Jorge Morales, Marisela
spellingShingle	Qi, Jia Zhang, Shiliang Wang, Hui-Ling Barker, David J. Miranda-Barrientos, Jorge Morales, Marisela VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons
author_facet	Qi, Jia Zhang, Shiliang Wang, Hui-Ling Barker, David J. Miranda-Barrientos, Jorge Morales, Marisela
author_sort	Qi, Jia
title	VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons
title_short	VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons
title_full	VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons
title_fullStr	VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons
title_full_unstemmed	VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons
title_sort	vta glutamatergic inputs to nucleus accumbens drive aversion by acting on gabaergic interneurons
description	The ventral tegmental area (VTA) is best known for its dopamine neurons, some of which project to nucleus accumbens (nAcc). However, the VTA also has glutamatergic neurons that project to nAcc. The function of the mesoaccumbens-glutamatergic pathway remains unknown. Here, we report that nAcc photoactivation of mesoaccumbens-glutamatergic fibers promotes aversion. Although we found that these mesoaccumbens-glutamate-fibers lack GABA, the aversion evoked by their photoactivation depends on glutamate and GABA receptor signaling, and not on dopamine receptor signaling. We found that mesoaccumbens-glutamatergic-fibers establish multiple asymmetric synapses on single parvalbumin-GABAergic interneurons, and that nAcc photoactivation of these fibers drives AMPA-mediated cellular firing of parvalbumin-GABAergic interneurons. These parvalbumin-GABAergic-interneurons, in turn, inhibit nAcc medium spiny output neurons, as such, controlling inhibitory neurotransmission within nAcc. The mesoaccumbens-glutamatergic pathway is the first glutamatergic input to nAcc shown to mediate aversion, instead of reward, and the first pathway shown to establish excitatory synapses on nAcc parvalbumin-GABAergic interneurons.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846550/
_version_	1613571473654415360

VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons

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