Nucleus accumbens medium spiny neurons subtypes signal both reward and aversion

被引:148
作者
Soares-Cunha, Carina [1 ,2 ]
de Vasconcelos, Nivaldo A. P. [1 ,2 ,3 ,4 ]
Coimbra, Barbara [1 ,2 ]
Domingues, Ana Veronica [1 ,2 ]
Silva, Joana M. [1 ,2 ]
Loureiro-Campos, Eduardo [1 ,2 ]
Gaspar, Rita [1 ,2 ,5 ,6 ]
Sotiropoulos, Ioannis [1 ,2 ]
Sousa, Nuno [1 ,2 ,7 ]
Rodrigues, Ana Joao [1 ,2 ,7 ]
机构
[1] Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga, Portugal
[2] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal
[3] Fed Univ Pernambuco UFPE, Phys Dept, BR-50670901 Recife, PE, Brazil
[4] Fed Univ Pernambuco UFPE, Dept Biomed Engn, BR-50670901 Recife, PE, Brazil
[5] Univ Coimbra, Fac Med, Coimbra Inst Clin & Biomed Res iCBR, Coimbra, Portugal
[6] Univ Coimbra, Ctr Innovat Biomed & Biotechnol CIBB, Coimbra, Portugal
[7] Clin Acad Ctr Braga 2CA, Braga, Portugal
关键词
VENTRAL TEGMENTAL AREA; DOPAMINE NEURONS; BEHAVIORAL SENSITIZATION; DISTINCT SUBPOPULATIONS; RECEPTOR MODULATION; STRIATAL NEURONS; D2; RECEPTORS; GABA NEURONS; IN-VIVO; COCAINE;
D O I
10.1038/s41380-019-0484-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 kappa -opioid receptors in the VTA (but not in VP) abolishes the behavioral effects induced by D1-MSN prolonged stimulation. In turn, blocking delta -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.
引用
收藏
页码:3241 / 3255
页数:15
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