Hall Brandon J, Abreu-Villaça Yael, Cauley Marty, Junaid Shaqif, White Hannah, Kiany Abtin, Levin Edward D
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
Neuropharmacology. 2017 May 1;117:106-113. doi: 10.1016/j.neuropharm.2017.01.019. Epub 2017 Jan 26.
Sex differences in cognitive processing and function have been documented in human and animal studies. Females have been found to perform better than males on non-spatial memory tasks, while males tend to outperform females on spatial memory tasks. The neural mechanisms underlying these sexual dimorphisms are unclear. However, it is known that the cholinergic system is critically involved in memory processes, and there are notable differences between males and females in cholinergic system function and receptor expression. In particular, there are sex differences in the processing of information in the frontal cortex and hippocampus. In this study, we examined the roles of muscarinic and nicotinic acetylcholine receptors in the medial frontal cortex (MfC) and ventral hippocampus (VH) on spatial working memory in male and female rats. Local infusions of scopolamine (SCOP) and mecamylamine (MEC) (10, 20, 50 μg/side) were used to antagonize these receptors in each respective brain region during performance in the 16-arm radial arm maze. Infusions of SCOP into the VH caused a significant increase in memory errors in female rats, but had no significant effect on males, while infusions of MEC into the VH had no effect on either sex. Infusions of both SCOP (50 μg/side) and MEC (20 μg/side) into the MfC caused working memory impairments in both sexes. These results show that muscarinic acetylcholine receptors in the VH are differentially vulnerable to spatial memory impairments in females. Ventral hippocampal muscarinic acetylcholine receptors may play a key role in male-female differences in spatial memory.
人类和动物研究均已证实认知加工和功能存在性别差异。研究发现，在非空间记忆任务中，雌性的表现优于雄性，而在空间记忆任务中，雄性往往比雌性表现更好。这些性别差异背后的神经机制尚不清楚。然而，已知胆碱能系统在记忆过程中起关键作用，并且雄性和雌性在胆碱能系统功能和受体表达方面存在显著差异。特别是，额叶皮质和海马体在信息处理方面存在性别差异。在本研究中，我们研究了毒蕈碱型和烟碱型乙酰胆碱受体在雄性和雌性大鼠内侧额叶皮质（MfC）和腹侧海马体（VH）对空间工作记忆中的作用。在16臂放射状迷宫实验过程中，通过在每个相应脑区局部注射东莨菪碱（SCOP）和美加明（MEC）（10、20、50μg/侧）来拮抗这些受体。向VH注射SCOP会使雌性大鼠的记忆错误显著增加，但对雄性大鼠没有显著影响，而向VH注射MEC对两性均无影响。向MfC注射SCOP（50μg/侧）和MEC（20μg/侧）均会导致两性的工作记忆受损。这些结果表明，VH中的毒蕈碱型乙酰胆碱受体对雌性空间记忆障碍的易感性存在差异。腹侧海马体毒蕈碱型乙酰胆碱受体可能在空间记忆的性别差异中起关键作用。
