Contributions of nucleus accumbens dopamine to cognitive flexibility.
Contributions of nucleus accumbens dopamine to cognitive flexibility.
复制标题
DOI：
10.1111/ejn.14152
复制
发表时间：
2019-08
期刊：
影响因子：
--
通讯作者：
Holmes A
中科院分区：
文献类型：
--
作者：
Radke AK;Kocharian A;Covey DP;Lovinger DM;Cheer JF;Mateo Y;Holmes A
有令人信服的证据表明，中脑多巴胺（DA）神经元及其向腹侧纹状体的投射提供了一种机制，可以激发寻求奖励的行为，并利用有关意外奖励（预测错误，RPE）的信息来指导基于当前而不是历史结果的行为。当这种机制在成瘾中受到损害时，它可能会产生适应不良的行为模式，在面对相反的信息甚至不利的后果时仍然顽固不化。尽管如此，DA能对依赖于灵活更新刺激-奖励关系的能力的行为任务的表现的贡献仍然不完全理解。在目前的研究中，我们使用的歧视和逆转范例，监测亚秒DA释放在小鼠NAc核心（NAc）使用在体内快速扫描循环伏安法（FSCV）。我们观察到选择后阶段NAc DA释放的升高;然而，增加DA瞬变仅在小鼠对新奖励刺激做出反应时的早期逆转期间明显。基于这一发现，我们使用体内光遗传学（盐视紫红质（eNpHR3.0））光沉默和（视紫红质2（ChR 2））光刺激来评估操纵NAc中的VTA-DA能纤维对逆转性能的影响。在早期逆转过程中，光沉默VTA→NAc DA能通路增加了错误，而光刺激并没有明显影响行为。两者合计，这些数据提供了额外的证据，NAC DA释放的重要性，作为神经基质支持调整后，在预期的刺激奖励意外事件的切换学习行为。这些发现可能对进一步理解DA在成瘾特征的持续性、适应不良决策中的作用产生影响。亚秒多巴胺（DA）的释放在丘脑核核心（NAc）的监测，使用快速扫描循环伏安法在歧视和逆转学习。在早期逆转过程中观察到阶段性DA释放的选择后升高，而VTA-DA能纤维的光沉默破坏了性能。这些数据提供了额外的证据，NAc DA释放的重要性，作为神经基质支持学习行为后，在预期的刺激奖励意外切换。
There is compelling evidence that midbrain dopamine (DA) neurons and their projections to the ventral striatum provide a mechanism for motivating reward-seeking behavior, and for utilizing information about unexpected rewards (prediction errors, RPEs) to guide behavior based on current, rather than historical, outcomes. When this mechanism is compromised in addictions, it may produce patterns of maladaptive behavior that remain obdurate in the face of contrary information and even adverse consequences. Nonetheless, DAergic contributions to performance on behavioral tasks that rely on an ability to flexibly update stimulus-reward relationships remains incomplete understood. In the current study, we used a discrimination and reversal paradigm to monitor subsecond DA release in mouse NAc core (NAc) using in vivo fast-scan cyclic voltammetry (FSCV). We observed post-choice elevations in phasic NAc DA release; however, increased DA transients were only evident during early reversal when mice made responses at the newly-rewarded stimulus. Based on this finding, we used in vivo optogenetic (halorhodopsin (eNpHR3.0)) photosilencing and (Channelrhodopsin2 (ChR2)) photostimulation to assess the effects of manipulating VTA-DAergic fibers in the NAc on reversal performance. Photosilencing the VTA→NAc DAergic pathway during early reversal increased errors, while photostimulation did not demonstrably affect behavior. Taken together, these data provide additional evidence of the importance of NAc DA release as a neural substrate supporting adjustments in learned behavior after a switch in expected stimulus-reward contingencies. These findings have possible implications for furthering understanding the role of DA in persistent, maladaptive decision-making characterizing addictions. Subsecond dopamine (DA) release in the nucleus accumbens core (NAc) was monitored using fast-scan cyclic voltammetry during discrimination and reversal learning. Post-choice elevations in phasic DA release were observed during early reversal while photosilencing of VTA-DAergic fibers disrupted performance. These data provide additional evidence of the importance of NAc DA release as a neural substrate supporting learned behavior after a switch in expected stimulus-reward contingencies.
登录
查看更多内容
影响因子：
64.8
作者：
Flagel SB;Clark JJ;Robinson TE;Mayo L;Czuj A;Willuhn I;Akers CA;Clinton SM;Phillips PE;Akil H
通讯作者：
Akil H
影响因子：
48
作者：
Clark, Jeremy J.;Sandberg, Stefan G.;Wanat, Matthew J.;Gan, Jerylin O.;Horne, Eric A.;Hart, Andrew S.;Akers, Christina A.;Parker, Jones G.;Willuhn, Ingo;Martinez, Vicente;Evans, Scott B.;Stella, Nephi;Phillips, Paul E. M.
通讯作者：
Phillips, Paul E. M.
DOI：
10.1523/jneurosci.5119-12.2013
发表时间：
2013-02-20
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Clark JJ;Collins AL;Sanford CA;Phillips PE
通讯作者：
Phillips PE
影响因子：
10.6
作者：
Day, Jeremy J.;Jones, Joshua L.;Wightman, R. Mark;Carelli, Regina M.
通讯作者：
Carelli, Regina M.
DOI：
10.1523/jneurosci.2246-11.2011
发表时间：
2011-07-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Adamantidis AR;Tsai HC;Boutrel B;Zhang F;Stuber GD;Budygin EA;Touriño C;Bonci A;Deisseroth K;de Lecea L
通讯作者：
de Lecea L