Moderate Prenatal Alcohol Exposure Impairs Visual-Spatial Discrimination in a Sex-Specific Manner: Effects of Testing Order and Difficulty on Learning Performance.
Moderate Prenatal Alcohol Exposure Impairs Visual-Spatial Discrimination in a Sex-Specific Manner: Effects of Testing Order and Difficulty on Learning Performance.
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DOI：
10.1111/acer.14426
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Brigman JL
中科院分区：
文献类型：
--
作者：
Kenton JA;Castillo VK;Kehrer PE;Brigman JL
在发育过程中暴露于高水平的酒精会导致神经发生的改变和大脑依赖性学习的缺陷。有证据表明，怀孕期间即使是更适度的饮酒也会对后代的认知功能产生负面影响。评估损伤的方法在物种之间差异很大，使临床前发现转化为潜在治疗方法变得复杂。我们已经证明了实用的触摸屏操作措施评估小鼠海马功能。在这里，我们整合了一个完善的“在黑暗中饮酒”暴露模型，产生可靠的，但更温和的，产妇中毒的水平与试验独特的，延迟的非匹配位置（TUNEL）任务，检查产前酒精暴露（PAE）的影响，直接类似于临床评估中使用的行为。在触摸屏操作系统中，训练PAE和SAC后代小鼠在10个可能的空间位置（2×5网格）之一中触摸单个视觉刺激（“样本阶段”）。在延迟之后，动物同时呈现原始刺激和在新位置的奖励刺激（“选择阶段”）。PAE和糖精（SAC）对照小鼠进行了一系列问题的训练，这些问题通过减少样品和选择刺激之间的分离来系统地增加难度。接下来，对单独的PAE和SAC动物队列进行简短的训练，然后在具有挑战性的变体上进行测试，其中分离和延迟随每次试验而变化。我们发现，PAE小鼠通常能够在与SAC对照小鼠相似的水平上进行逐渐更困难的分离。当测试的最困难的不可预测的变量立即，PAE表现出性别特异性赤字与PAE女性表现更差，在长时间的延迟。总之，这些数据证明了TUNEL任务用于检查海马功能中PAE相关改变的实用性，并强调了在这些模型中检查性别与治疗相互作用的必要性。
Exposure to high levels of alcohol during development leads to alterations in neurogenesis and deficits in hippocampal-dependent learning. Evidence suggests that even more moderate alcohol consumption during pregnancy can have negative impacts on the cognitive function of offspring. Methods for assessing impairments differ greatly across species, complicating translation of preclinical findings into potential therapeutics. We have demonstrated the utility of a touchscreen operant measure for assessing hippocampal function in mice. Here, we integrated a well-established ‘drinking-in-the-dark’ exposure model that produces reliable, but more moderate, levels of maternal intoxication with a trial unique, delayed nonmatching-to-location (TUNL) task to examine the effects of prenatal alcohol exposure (PAE) on hippocampal-sensitive behavior directly analogous to those used in clinical assessment. PAE and SAC offspring mice were trained to touch a single visual stimulus (“sample phase”) in one of 10 possible spatial locations (2×5 grid) in a touch-screen operant system. After a delay, animals were simultaneously presented with the original stimulus and a rewarded stimulus in a novel location (“choice phase”). PAE and saccharin (SAC) control mice were trained on a series of problems that systematically increased the difficulty by decreasing the separation between the sample and choice stimuli. Next, a separate cohort of PAE and SAC animals were given a brief training and then tested on a challenging variant where both the separation and delay varied with each trial. We found that PAE mice were generally able to perform at levels similar to SAC control mice at progressively more difficult separations. When tested on the most difficult unpredictable variant immediately, PAE showed a sex specific deficit with PAE females performing worse during long delays. Taken together, these data demonstrate the utility of the TUNL task for examining PAE related alterations in hippocampal function and underline the need to examine sex-by-treatment interactions in these models.
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影响因子：
2.7
作者：
Hamilton, Derek A.;Barto, Daniel;Rodriguez, Carlos I.;Magcalas, Christy M.;Fink, Brandi C.;Rice, James P.;Bird, Clark W.;Davies, Suzy;Savage, Daniel D.
通讯作者：
Savage, Daniel D.
精神分裂症认知临床前模型的新转化测定：小鼠和大鼠的触摸屏测试方法。
影响因子：
4.7
作者：
Bussey TJ;Holmes A;Lyon L;Mar AC;McAllister KA;Nithianantharajah J;Oomen CA;Saksida LM
通讯作者：
Saksida LM
影响因子：
3.2
作者：
Dodge, Neil C.;Thomas, Kevin G. F.;Jacobson, Sandra W.
通讯作者：
Jacobson, Sandra W.
DOI：
10.1111/j.1469-7610.2008.01990.x
发表时间：
2009-06-01
影响因子：
7.6
作者：
Green, C. R.;Mihic, A. M.;Reynolds, J. N.
通讯作者：
Reynolds, J. N.
影响因子：
2.9
作者：
Herremans, AHJ;Hijzen, TH;Slangen, JL
通讯作者：
Slangen, JL