Anterior thalamic circuits crucial for working memory.
Anterior thalamic circuits crucial for working memory.
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DOI：
10.1073/pnas.2118712119
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发表时间：
2022-05-17
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
随着年龄的增长，前丘脑表现出显着的功能变化。虽然它与认知功能有关，但与工作记忆相关的具体电路仍然未知。这项研究的意义有三：首先，丘脑前核的前腹侧细分对于工作记忆的维持是必要的；其次，老年小鼠的丘脑前腹神经元兴奋性下降，这与工作记忆障碍有关；第三，激活老年小鼠的前腹侧丘脑神经元足以改善其工作记忆。丘脑前核（ATN）结构和功能连接的改变与衰老过程中认知能力的下降有关。然而，有助于更高认知功能的 ATN 回路仍未得到充分研究。我们发现 ATN 的前腹侧 (AV) 细分在空间工作记忆任务的维持阶段是必要的。该功能涉及 AV→parasububiculum (PaS)→内嗅皮层 (EC) 回路。老年小鼠表现出空间工作记忆缺陷，这与房室神经元兴奋性下降有关。激活老年小鼠的 AV 神经元或 AV→PaS 回路足以挽救其工作记忆性能。此外，获救的老年小鼠在前额皮质（PFC）中表现出行为诱导的神经元活动得到改善，PFC是工作记忆过程的关键部位。尽管直接激活老年小鼠的 PFC 神经元也挽救了它们的工作记忆表现，但我们发现这些动物表现出焦虑水平增加，而对老年小鼠进行 AV→PaS 回路操作则并非如此。这些结果表明，针对衰老过程中的 AV 丘脑可能不仅有益于认知功能，而且与直接 PFC 操作相比，这种方法可能会产生更少的意外影响。
Anterior thalamus exhibits significant functional changes with increasing age. While it has been associated with cognitive functions, the specific circuitry relevant for working memory remains unknown. The significance of this study is threefold: First, the anteroventral subdivision of anterior thalamic nuclei is necessary for working memory maintenance; second, aged mice showed a decrease in the excitability of anteroventral thalamic neurons, which correlated with a working memory impairment; and third, activating anteroventral thalamic neurons in aged mice was sufficient to improve their working memory. Alterations in the structure and functional connectivity of anterior thalamic nuclei (ATN) have been linked to reduced cognition during aging. However, ATN circuits that contribute to higher cognitive functions remain understudied. We found that the anteroventral (AV) subdivision of ATN is necessary specifically during the maintenance phase of a spatial working memory task. This function engages the AV→parasubiculum (PaS)→entorhinal cortex (EC) circuit. Aged mice showed a deficit in spatial working memory, which was associated with a decrease in the excitability of AV neurons. Activation of AV neurons or the AV→PaS circuit in aged mice was sufficient to rescue their working memory performance. Furthermore, rescued aged mice showed improved behavior-induced neuronal activity in prefrontal cortex (PFC), a critical site for working memory processes. Although the direct activation of PFC neurons in aged mice also rescued their working memory performance, we found that these animals exhibited increased levels of anxiety, which was not the case for AV→PaS circuit manipulations in aged mice. These results suggest that targeting AV thalamus in aging may not only be beneficial for cognitive functions but that this approach may have fewer unintended effects compared to direct PFC manipulations.
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影响因子：
5.7
作者：
Hughes, Emer J.;Bond, Jacqueline;Svrckova, Patricia;Makropoulos, Antonis;Ball, Gareth;Sharp, David J.;Edwards, A. David;Hajnal, Joeseph V.;Counsell, Serena J.
通讯作者：
Counsell, Serena J.
影响因子：
10.6
作者：
Davidson, RJ
通讯作者：
Davidson, RJ
影响因子：
2
作者：
Savage, Lisa M.;Hall, Joseph M.;Vetreno, Ryan P.
通讯作者：
Vetreno, Ryan P.
影响因子：
14.5
作者：
BADDELEY, AD;BRESSI, S;SPINNLER, H
通讯作者：
SPINNLER, H
影响因子：
3.3
作者：
Harada CN;Natelson Love MC;Triebel KL
通讯作者：
Triebel KL