Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada.
Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada
eNeuro. 2022 May 12;9(3). doi: 10.1523/ENEURO.0054-22.2022. Print 2022 May-Jun.
Adult neurogenesis modifies hippocampal circuits and behavior, but removing newborn neurons does not consistently alter spatial processing, a core function of the hippocampus. Additionally, little is known about sex differences in neurogenesis since few studies have compared males and females. Since adult-born neurons regulate the stress response, we hypothesized that spatial functions may be more prominent under aversive conditions and may differ between males and females given sex differences in stress responding. We therefore trained intact and neurogenesis-deficient rats in the spatial water maze at temperatures that vary in their degree of aversiveness. In the standard water maze, ablating neurogenesis did not alter spatial learning in either sex. However, in cold water, ablating neurogenesis had divergent sex-dependent effects: relative to intact rats, male neurogenesis-deficient rats were slower to escape the maze and female neurogenesis-deficient rats were faster. Neurogenesis promoted temperature-related changes in search strategy in females, but it promoted search strategy stability in males. Females displayed greater recruitment (Fos expression) of the dorsal hippocampus than males, particularly in cold water. However, blocking neurogenesis did not alter Fos expression in either sex. Finally, morphologic analyses revealed greater experience-dependent plasticity in males. Adult-born neurons in males and females had similar morphology at baseline but training increased spine density and reduced presynaptic terminal size, specifically in males. Collectively, these findings indicate that adult-born neurons contribute to spatial learning in stressful conditions and they provide new evidence for sex differences in their behavioral functions.
成人神经发生会改变海马体回路和行为，但去除新生神经元并不总是改变空间处理，这是海马体的核心功能。此外，由于很少有研究比较男性和女性，因此对神经发生中的性别差异知之甚少。由于成年产生的神经元调节应激反应，我们假设空间功能在恶劣条件下可能更为突出，并且由于应激反应中的性别差异，可能在男性和女性之间存在差异。因此，我们在空间水迷宫中训练完整和神经发生缺陷的大鼠，温度在其厌恶程度上有所不同。在标准水迷宫中，神经发生的缺失不会改变两性的空间学习。然而，在冷水中，神经发生的缺失具有性别依赖性的不同影响：与完整的大鼠相比，雄性神经发生缺陷的大鼠逃离迷宫的速度较慢，而雌性神经发生缺陷的大鼠速度较快。神经发生促进了女性在搜索策略方面与温度相关的变化，但在男性中促进了搜索策略的稳定性。与男性相比，女性表现出更大的（Fos 表达）背侧海马体募集，尤其是在冷水中。然而，在两性中，神经发生的缺失并未改变 Fos 表达。最后，形态分析显示男性表现出更大的经验依赖性可塑性。雄性和雌性中的成年产生的神经元在基线时具有相似的形态，但训练增加了树突棘密度并减少了突触前末端的大小，特别是在雄性中。总之，这些发现表明成年产生的神经元有助于在应激条件下的空间学习，并为其行为功能中的性别差异提供了新的证据。
