Chemogenetic inhibition of prefrontal projection neurons constrains top-down control of attention in young but not aged rats.
Chemogenetic inhibition of prefrontal projection neurons constrains top-down control of attention in young but not aged rats.
复制标题
前额叶投射神经元的化学发生抑制抑制年轻而非老年大鼠的注意力自上而下控制。
DOI：
10.1007/s00429-021-02336-2
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发表时间：
2021-09
影响因子：
3.1
通讯作者：
Parikh V
中科院分区：
文献类型：
--
作者：
Duggan MR;Joshi S;Strupp J;Parikh V
前额叶皮层（PFC）控制着自上而下的注意力控制，并且在衰老过程中变得脆弱。皮质重组增加PFC招聘建议占功能补偿。在这里，我们假设减少PFC输出会对年轻和老年大鼠的注意力产生不同的影响，后者表现出更强劲的性能下降。利用涉及仅由设计药物激活的设计受体的化学遗传学方法来确定沉默PFC投射神经元对执行操作性注意任务的大鼠的影响。在所有的行为测试中，视觉干扰物被提出来征税的注意力资源。在对照条件下，老年大鼠表现出的障碍，从非信号事件的持续时间最短的歧视信号。令人惊讶的是，PFC输出神经元的化学发生抑制并没有使老年动物的表现恶化。相反，注意力的能力显着受损，观察到在年轻受试者这样的操作。考虑到PFC投射基底前脑胆碱能神经元参与自上而下的注意力调节，进行了电流记录，以测量在一个单独的队列的年轻和老年大鼠前额叶胆碱能传递的变化。虽然PFC沉默导致了一个强大的衰减强直胆碱能信号在不同年龄组，产生阶段性胆碱能瞬变的能力受损，只有年轻的动物。总的来说，我们的研究结果表明，PFC介导的自上而下的控制的注意力和胆碱能系统在老龄化的效率降低，PFC输出神经元的活动并不反映在老年大鼠的补偿，至少在注意力领域。
The prefrontal cortex (PFC) governs top-down control of attention and is known to be vulnerable in aging. Cortical reorganization with increased PFC recruitment is suggested to account for functional compensation. Here, we hypothesized that reduced PFC output would exert differential effects on attentional capacities in young and aged rats, with the latter exhibiting more robust decline in performance. A chemogenetic approach involving Designer Receptors Exclusively Activated by Designer Drugs was utilized to determine the impact of silencing PFC projection neurons in rats performing an operant attention task. Visual distractors were presented in all behavioral testing sessions to tax attentional resources. Under control conditions, aged rats exhibited impairments in discriminating signals with the shortest duration from non-signal events. Surprisingly, chemogenetic inhibition of PFC output neurons did not worsen performance amongst aged animals. Conversely, significant impairments in attentional capacities were observed in young subjects following such manipulation. Given the involvement of PFC-projecting basal forebrain cholinergic neurons in top-down regulation of attention, amperometric recordings were conducted to measure alterations in prefrontal cholinergic transmission in a separate cohort of young and aged rats. While PFC silencing resulted in a robust attenuation of tonic cholinergic signaling across age groups, the capacity of generate phasic cholinergic transients was impaired only amongst young animals. Collectively, our findings suggest reduced efficiency of PFC-mediated top-down control of attention and cholinergic system in aging, and that activity of PFC output neurons does not reflect compensation in aged rats, at least in the attention domain.
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影响因子：
8.2
作者：
Fortenbaugh FC;DeGutis J;Germine L;Wilmer JB;Grosso M;Russo K;Esterman M
通讯作者：
Esterman M
影响因子：
3.7
作者：
Dalley, JW;Theobald, DE;Robbins, TW
通讯作者：
Robbins, TW
影响因子：
3.7
作者：
Davis, Simon W.;Dennis, Nancy A.;Cabeza, Roberto
通讯作者：
Cabeza, Roberto
DOI：
10.1038/npp.2010.104
发表时间：
2011-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.6
作者：
Jendryka, Martin;Palchaudhuri, Monika;Pekcec, Anton
通讯作者：
Pekcec, Anton