Mooney-Leber Sean M, Zeid Dana, Garcia-Trevizo Prescilla, Seemiller Laurel R, Bogue Molly A, Grubb Stephen C, Peltz Gary, Gould Thomas J
Department of Psychology, University of Wisconsin-Stevens Point, Stevens Point, WI, United States.
Department of Biobehavioral Health, The Pennsylvania State University, State College, PA, United States.
Front Psychiatry. 2021 Oct 18;12:737897. doi: 10.3389/fpsyt.2021.737897. eCollection 2021.
Learning is a critical behavioral process that is influenced by many neurobiological systems. We and others have reported that acetylcholinergic signaling plays a vital role in learning capabilities, and it is especially important for contextual fear learning. Since cholinergic signaling is affected by genetic background, we examined the genetic relationship between activity levels of acetylcholinesterase (AChE), the primary enzyme involved in the acetylcholine metabolism, and learning using a panel of 20 inbred mouse strains. We measured conditioned fear behavior and AChE activity in the dorsal hippocampus, ventral hippocampus, and cerebellum. Acetylcholinesterase activity varied among inbred mouse strains in all three brain regions, and there were significant inter-strain differences in contextual and cued fear conditioning. There was an inverse correlation between fear conditioning outcomes and AChE levels in the dorsal hippocampus. In contrast, the ventral hippocampus and cerebellum AChE levels were not correlated with fear conditioning outcomes. These findings strengthen the link between acetylcholine activity in the dorsal hippocampus and learning, and they also support the premise that the dorsal hippocampus and ventral hippocampus are functionally discrete.
学习是一个受多种神经生物学系统影响的关键行为过程。我们和其他人已经报道，乙酰胆碱能信号在学习能力中起着至关重要的作用，对情境恐惧学习尤为重要。由于胆碱能信号受遗传背景影响，我们使用一组20个近交系小鼠品系研究了参与乙酰胆碱代谢的主要酶——乙酰胆碱酯酶（AChE）的活性水平与学习之间的遗传关系。我们测量了背侧海马体、腹侧海马体和小脑中的条件性恐惧行为和AChE活性。在所有三个脑区中，近交系小鼠品系间的乙酰胆碱酯酶活性存在差异，并且在情境性和线索性恐惧条件反射中存在显著的品系间差异。背侧海马体中的恐惧条件反射结果与AChE水平呈负相关。相比之下，腹侧海马体和小脑的AChE水平与恐惧条件反射结果无关。这些发现加强了背侧海马体中乙酰胆碱活性与学习之间的联系，也支持了背侧海马体和腹侧海马体在功能上是离散的这一前提。
