Prefrontal deep projection neurons enable cognitive flexibility via persistent feedback monitoring
Prefrontal deep projection neurons enable cognitive flexibility via persistent feedback monitoring
复制标题
前额深投射神经元通过持续反馈监控实现认知灵活性
作者：
Timothy Spellman;Malka Svei;Jesse Kaminsky;Gabriela Manzano;Conor Liston
认知灵活性，即根据变化的刺激-反应-奖励关系改变策略的能力，是获得和执行学习行为的关键工具。为了适应新的、不确定的或动态的环境，通常需要放弃以前成功的规则，并在试错的基础上探索新的规则。认知灵活性的一种形式，通常被称为集合转移，需要忽略先前相关的刺激特征，而支持新的相关特征。先前的研究表明，成功的定势转换行为涉及前额叶皮层（PFC），定势转换行为的障碍与多种精神疾病有关。尽管这种行为的翻译重要性，但目前仍不清楚PFC中的哪些细胞类型负责将对设置转移至关重要的信息传递到下游大脑区域。为了解决这个问题，我们使用了一种新的设置在头部固定的小鼠转移任务，以测试两个主要的PFC预测，皮质-纹状体和皮质-丘脑途径，在设置转移的作用。使用光遗传学和双光子钙成像，我们发现这些细胞类型稳健而持久地编码来自最近试验结果的反馈，并且在试验间隔期间两种细胞类型的活动对于成功切换任务规则至关重要。此外，我们发现，这两种细胞类型显示出拓扑梯度，神经元位于更远离软膜表面代表更多的任务关键信息。总之，这些研究结果表明，深PFC投射神经元通过试验反馈监测实现设置转换。
Cognitive flexibility, the ability to alter one’s strategy in light of changing stimulus-response-reward relationships, is a critical tool for acquiring and executing learned behavior. In order to adapt to novel, uncertain, or dynamic contexts, it is often necessary to abandon previously successful rules, and explore new rules, based on trial and error. One form of cognitive flexibility, commonly referred to as set-shifting, entails ignoring a previously relevant stimulus feature in favor of a newly relevant features. Successful performance of set-shifting behavior has been shown through previous work to involve the prefrontal cortex (PFC), and impairments in set-shifting behavior are associated with multiple psychiatric disorders. In spite of the translational importance of this behavior, it remains unclear which cell types within PFC are responsible for conveying information critical to set-shifting to downstream brain regions. To address this question, we used a novel set-shifting task in head-fixed mice to test the role of two major PFC projections, the cortico-striatal and cortico-thalamic pathways, in set-shifting. Using optogenetics and 2-photon calcium imaging, we found that these cell types robustly and persistently encoded feedback from the outcomes of recent trials, and that the activity of both cell types during the inter-trial interval was critical to successfully switching between task rules. Moreover, we found that both cell types displayed a topological gradient, with neurons located further from the pial surface representing more task-critical information. Together, these findings suggest that deep PFC projection neurons enable set-shifting through trial feedback monitoring.
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DOI：
10.1073/pnas.0603081103
发表时间：
2006-06-06
影响因子：
11.1
作者：
Hnasko, Thomas S.;Perez, Francisco A.;Palmiter, Richard D.
通讯作者：
Palmiter, Richard D.
DOI：
10.1073/pnas.1114415109
发表时间：
2012-03-27
影响因子：
11.1
作者：
Hyman, James M.;Ma, Liya;Seamans, Jeremy K.
通讯作者：
Seamans, Jeremy K.
影响因子：
0.8
作者：
J. Turner;Jennifer L. Parrish;L. Hughes;L. Toth;D. Caspary
通讯作者：
J. Turner;Jennifer L. Parrish;L. Hughes;L. Toth;D. Caspary
影响因子：
56.9
作者：
DENK, W;STRICKLER, JH;WEBB, WW
通讯作者：
WEBB, WW