Miranda-Barrientos Jorge, Adiraju Suhaas, Rehg Jason J, Hallock Henry L, Li Ye, Carr Gregory V, Martinowich Keri
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA.
Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
bioRxiv. 2024 Jul 26:2024.07.26.605300. doi: 10.1101/2024.07.26.605300.
Sustained attention, the ability to focus on a stimulus or task over extended periods, is crucial for higher level cognition, and is impaired in individuals diagnosed with neuropsychiatric and neurodevelopmental disorders, including attention-deficit/hyperactivity disorder, schizophrenia, and depression. Translational tasks like the rodent continuous performance test (rCPT) can be used to study the cellular mechanisms underlying sustained attention. Accumulating evidence points to a role for the prelimbic cortex (PrL) in sustained attention, as electrophysiological single unit and local field (LFPs) recordings reflect changes in neural activity in the PrL in mice performing sustained attention tasks. While the evidence correlating PrL electrical activity with sustained attention is compelling, limitations inherent to electrophysiological recording techniques, including low sampling in single unit recordings and source ambivalence for LFPs, impede the ability to fully resolve the cellular mechanisms in the PrL that contribute to sustained attention. endoscopic calcium imaging using genetically encoded calcium sensors in behaving animals can address these questions by simultaneously recording up to hundreds of neurons at single cell resolution. Here, we used endoscopic calcium imaging to record patterns of neuronal activity in PrL neurons using the genetically encoded calcium sensor GCaMP6f in mice performing the rCPT at three timepoints requiring differing levels of cognitive demand and task proficiency. A higher proportion of PrL neurons were recruited during correct responses in sessions requiring high cognitive demand and task proficiency, and mice intercalated non-responsive-disengaged periods with responsive-engaged periods that resemble attention lapses. During disengaged periods, the correlation of calcium activity between PrL neurons was higher compared to engaged periods, suggesting a neuronal network state change during attention lapses in the PrL. Overall, these findings illustrate that cognitive demand, task proficiency, and task engagement differentially recruit activity in a subset of PrL neurons during sustained attention.
持续注意力，即长时间专注于一种刺激或任务的能力，对高级认知至关重要，而在被诊断患有神经精神和神经发育障碍的个体中会受到损害，这些障碍包括注意力缺陷多动障碍、精神分裂症和抑郁症。像啮齿动物持续操作测试（rCPT）这样的转化任务可用于研究持续注意力背后的细胞机制。越来越多的证据表明前额叶皮质（PrL）在持续注意力中发挥作用，因为电生理单单位和局部场电位（LFP）记录反映了执行持续注意力任务的小鼠PrL中神经活动的变化。虽然将PrL电活动与持续注意力相关联的证据很有说服力，但电生理记录技术固有的局限性，包括单单位记录中的低采样率和LFP的源不确定性，阻碍了我们完全解析PrL中有助于持续注意力的细胞机制的能力。在行为动物中使用基因编码钙传感器进行内镜钙成像可以通过以单细胞分辨率同时记录多达数百个神经元来解决这些问题。在这里,我们使用内镜钙成像，在三个需要不同认知需求和任务熟练度水平的时间点，对执行rCPT的小鼠使用基因编码钙传感器GCaMP6f记录PrL神经元的神经活动模式。在需要高认知需求和任务熟练度的实验中，正确反应期间招募的PrL神经元比例更高，并且小鼠将无反应-脱离期与类似注意力 lapses 的有反应-参与期穿插起来。在脱离期，PrL神经元之间的钙活动相关性比参与期更高，这表明PrL在注意力 lapses 期间神经元网络状态发生了变化。总体而言，这些发现表明，在持续注意力过程中，认知需求、任务熟练度和任务参与度会在PrL神经元的一个子集中差异性地招募活动。
