Chemogenetic suppression of anterior cingulate cortical neurons projecting to the visual cortex disrupts attentional behavior in mice.
Chemogenetic suppression of anterior cingulate cortical neurons projecting to the visual cortex disrupts attentional behavior in mice.
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化学发生抑制的前扣带回皮质神经元投射到视觉皮质扰乱小鼠的注意行为。
DOI：
10.1002/npr2.12176
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发表时间：
2021-06
影响因子：
2.5
通讯作者：
Morishita H
中科院分区：
文献类型：
--
作者：
Norman KJ;Koike H;McCraney SE;Garkun Y;Bateh J;Falk EN;Im S;Caro K;Demars MP;Morishita H
注意是一个目标导向的认知过程，有助于从动态环境中发现与任务相关的感官刺激。众所周知，前扣带皮质区（ACA）在注意行为中起着关键作用，但介导注意的特定电路在很大程度上仍然未知。由于ACA调节视觉皮层（VIS）的感觉加工，我们的目的是验证一个假设，即从ACA到VIS的额顶向下神经元（ACAVIS）通过化学发生方法参与视觉注意行为。成年雄性小鼠被训练使用触屏系统完成5项选择的连续反应时间任务（5CSRTT）。采用交叉病毒方法在ACAVIS神经元中选择性表达由设计药物（iDREADD）或静态荧光团（mCherry）激活的抑制性设计受体。小鼠在5CSRTT测试前接受iDREADD配体（氯氮平-一氧化氮；CNO）或对照物（生理盐水）的平衡注射（i.p）。最后，小鼠在CNO或生理盐水给药后进行进行性比率试验和开放场试验。在5CSRTT中，ACAVIS神经元活性的化学发生抑制降低了正确的任务表现，主要是由于遗漏的增加和准确性的趋势下降，而与动机、冲动或强迫相关的行为结果没有改变。ACAVIS神经元抑制不影响累进比任务的断点和开阔场实验中的移动距离。CNO本身对表达mCherry‐小鼠的任务表现没有影响。这些结果表明，远程额觉ACAVIS投射神经元是自上而下的注意行为的关键参与者，可能是有益的治疗靶点。电路特异性化学发生沉默表明，从前扣带皮层向视觉区投射的额叶神经元对小鼠自上而下的注意行为控制至关重要。本研究表明，长程额叶感觉投射神经元是自上而下的注意行为的关键参与者，可能是一个有益的治疗靶点。
Attention is a goal‐directed cognitive process that facilitates the detection of task‐relevant sensory stimuli from dynamic environments. Anterior cingulate cortical area (ACA) is known to play a key role in attentional behavior, but the specific circuits mediating attention remain largely unknown. As ACA modulates sensory processing in the visual cortex (VIS), we aim to test a hypothesis that frontal top‐down neurons projecting from ACA to VIS (ACAVIS) contributes to visual attention behavior through chemogenetic approach. Adult, male mice were trained to perform the 5‐choice serial reaction time task (5CSRTT) using a touchscreen system. An intersectional viral approach was used to selectively express inhibitory designer receptors exclusively activated by designer drugs (iDREADD) or a static fluorophore (mCherry) in ACAVIS neurons. Mice received counterbalanced injections (i.p.) of the iDREADD ligand (clozapine‐N‐oxide; CNO) or vehicle (saline) prior to 5CSRTT testing. Finally, mice underwent progressive ratio testing and open field testing following CNO or saline administration. Chemogenetic suppression of ACAVIS neuron activity decreased correct task performance during the 5CSRTT mainly driven by an increase in omission and a trending decrease in accuracy with no change in behavioral outcomes associated with motivation, impulsivity, or compulsivity. Breakpoint during the progressive ratio task and distance moved in the open field test were unaffected by ACAVIS neuron suppression. CNO administration itself had no effect on task performance in mCherry‐expressing mice. These results identify long‐range frontal‐sensory ACAVIS projection neurons as a key enactor of top‐down attentional behavior and may serve as a beneficial therapeutic target. Circuit‐specific chemogenetic silencing demonstrated that frontal neurons projecting from anterior cingulate cortex to visual are essential for top‐down control of attention behavior in mice. This study suggests that long‐range frontal‐sensory projection neurons as a key enactor of top‐down attentional behavior and may serve as a beneficial therapeutic target.
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