Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/62385

TitleNucleus accumbens medium spiny neurons subtypes signal both reward and aversion
Author(s)Soares-Cunha, Carina
Vasconcelos, Nivaldo António Portela
Coimbra, Bárbara
Domingues, Ana Verónica
Silva, Joana M.
Loureiro-Campos, Eduardo
Gaspar, Rita
Sotiropoulos, I.
Sousa, Nuno
Rodrigues, Ana João
Issue date28-Aug-2019
JournalMolecular Psychiatry
CitationSoares-Cunha, C., de Vasconcelos, N. A., Coimbra, B., Domingues, A. V., et. al. (2019). Nucleus accumbens medium spiny neurons subtypes signal both reward and aversion. Molecular psychiatry, 1-15.
Abstract(s)Deficits in decoding rewarding (and aversive) signals are present in several neuropsychiatric conditions such as depression and addiction, emphasising the importance of studying the underlying neural circuits in detail. One of the key regions of the reward circuit is the nucleus accumbens (NAc). The classical view on the field postulates that NAc dopamine receptor D1-expressing medium spiny neurons (D1-MSNs) convey reward signals, while dopamine receptor D2-expressing MSNs (D2-MSNs) encode aversion. Here, we show that both MSN subpopulations can drive reward and aversion, depending on their neuronal stimulation pattern. Brief D1- or D2-MSN optogenetic stimulation elicited positive reinforcement and enhanced cocaine conditioning. Conversely, prolonged activation induced aversion, and in the case of D2-MSNs, decreased cocaine conditioning. Brief stimulation was associated with increased ventral tegmenta area (VTA) dopaminergic tone either directly (for D1-MSNs) or indirectly via ventral pallidum (VP) (for D1- and D2-MSNs). Importantly, prolonged stimulation of either MSN subpopulation induced remarkably distinct electrophysiological effects in these target regions. We further show that blocking κ-opioid receptors in the VTA (but not in VP) abolishes the behavioral effects induced by D1-MSN prolonged stimulation. In turn, blocking δ-opioid receptors in the VP (but not in VTA) blocks the behavioral effects elicited by D2-MSN prolonged stimulation. Our findings demonstrate that D1- and D2-MSNs can bidirectionally control reward and aversion, explaining the existence of controversial studies in the field, and highlights that the proposed striatal functional opposition needs to be reconsidered.
TypeArticle
URIhttp://hdl.handle.net/1822/62385
DOI10.1038/s41380-019-0484-3
ISSN1359-4184
e-ISSN1476-5578
Publisher versionhttps://www.nature.com/articles/s41380-019-0484-3
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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