Laboratory of Biological Psychology, University of Leuven, Belgium.
Behav Brain Res. 2012 Apr 1;229(1):250-6. doi: 10.1016/j.bbr.2011.12.030. Epub 2012 Jan 12.
Mouse models are increasingly used to investigate genetic contributions to developmental disorders in children, especially newborns. In particular, early cognitive assessment in newborn mice is critical to evaluate pediatric drug efficacy and toxicity. Unfortunately, methods for behavioral tests in newborn mice are scarce. Therefore, developing such tests for newborn mice is a priority challenge for neurogenetics and pharmacological research. The aim of the present study was to develop a conditioning method well suited to high-throughput cognitive screening in newborn mice. To this end, we developed an odor-preference conditioning test using ambient temperature as an unconditioned stimulus (US) and artificial odors as conditioned stimuli (CS). First, we showed that mouse pups move toward the thermoneutral temperature when offered a choice between a thermoneutral and cold environment, thus showing thermotaxis. Second, we conducted a classical conditioning paradigm in pups aged six to ten days. In terms of central nervous system development, this period corresponds to extreme prematurity to early post-term period in humans. During acquisition, the pups were alternatively exposed to odor CS paired with either cold or warm temperatures. Immediately after acquisition, the pups underwent a two-odor choice test, which showed preference for the odor previously paired with the warm temperature, thus showing conditioning. The proposed paradigm is easy to conduct, and requires modest experimenter interference. The method is well suited for high-throughput screening of early associative disorders in newborn mice.
小鼠模型越来越多地被用于研究儿童（尤其是新生儿）发育障碍的遗传因素。特别是，早期评估新生儿的认知能力对于评估儿科药物的疗效和毒性至关重要。不幸的是，针对新生小鼠的行为测试方法非常有限。因此，为新生小鼠开发此类测试是神经遗传学和药理学研究的首要挑战。本研究旨在开发一种非常适合于新生小鼠高通量认知筛选的条件反射方法。为此，我们开发了一种气味偏好条件反射测试，使用环境温度作为非条件刺激（US），并使用人工气味作为条件刺激（CS）。首先，我们表明，当提供热中性温度和冷环境之间的选择时，新生鼠会向热中性温度移动，从而表现出趋热性。其次，我们在 6 至 10 天大的幼鼠中进行了经典条件反射实验。就中枢神经系统发育而言，这段时期相当于人类的超早产到早期足月期。在获得阶段，幼鼠交替暴露于与冷或暖温度配对的气味 CS。获得后立即，幼鼠进行了双气味选择测试，显示对先前与温暖温度配对的气味的偏好，从而表现出条件反射。提出的方法易于实施，并且需要适度的实验者干扰。该方法非常适合于新生小鼠早期联想障碍的高通量筛选。
