Ribic Adema, McCoy Emily, Pendala Vyshnavi, Fariborzi Mona, Demir Lara, Buell Olivia, Fedde Samuel, Stinger Jacqueline, Elbaum Luciano, Holsworth Troy, Awude Philip Amenyo
University of Virginia.
Res Sq. 2024 Dec 11:rs.3.rs-5529783. doi: 10.21203/rs.3.rs-5529783/v1.
Preterm birth is a leading risk factor for atypicalities in cognitive and sensory processing, but it is unclear how prematurity impacts circuits that support these functions. To address this, we trained adult mice born a day early (preterm mice) on a visual discrimination task and found that they commit more errors and fail to achieve high levels of performance. Using , we found that the neurons in the primary visual cortex (V1) and the V1-projecting prefrontal anterior cingulate cortex (ACC) are hyper-responsive to the reward, reminiscent of cue processing in adolescence. Moreover, the non-rewarded cue fails to robustly activate the V1 and V1-projecting ACC neurons during error trials, in contrast to prefrontal fast-spiking (FS) interneurons which show elevated error-related activity, suggesting that preterm birth impairs the function of prefrontal circuits for error monitoring. Finally, environmental enrichment, a well-established paradigm that promotes sensory maturation, failed to improve the performance of preterm mice, suggesting limited capacity of early interventions for reducing the risk of cognitive deficits after preterm birth. Altogether, our study for the first time identifies potential circuit mechanisms of cognitive atypicalities in the preterm population and highlights the vulnerability of prefrontal circuits to advanced onset of extrauterine experience.
早产是认知和感觉处理异常的主要风险因素，但尚不清楚早产如何影响支持这些功能的神经回路。为了解决这个问题，我们对提前一天出生的成年小鼠（早产小鼠）进行视觉辨别任务训练，发现它们犯的错误更多，且无法达到高水平的表现。通过[具体方法未给出]，我们发现初级视觉皮层（V1）和投射到V1的前额叶前扣带回皮层（ACC）中的神经元对奖励反应过度，这让人联想到青春期的线索处理。此外，与前额叶快发放（FS）中间神经元在错误试验中显示出与错误相关的活动增加相反，在错误试验期间，无奖励线索未能有力地激活V1和投射到V1的ACC神经元，这表明早产会损害前额叶回路进行错误监测的功能。最后，环境丰富化是一种公认的促进感觉成熟的模式，但未能改善早产小鼠的表现，这表明早期干预降低早产出生后认知缺陷风险的能力有限。总之，我们的研究首次确定了早产人群认知异常的潜在神经回路机制，并突出了前额叶回路对宫外经历提前发生的脆弱性。
