Continuous neurogenesis in the adult forebrain is required for innate olfactory responses
Continuous neurogenesis in the adult forebrain is required for innate olfactory responses
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DOI：
10.1073/pnas.1018782108
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发表时间：
2011-05-17
影响因子：
11.1
通讯作者：
Kageyama, Ryoichiro
中科院分区：
文献类型：
--
作者：
Sakamoto, Masayuki;Imayoshi, Itaru;Kageyama, Ryoichiro
尽管成年神经发生在海马区依赖的学习和记忆中的功能意义已经被很好地记录下来，但这种神经发生在嗅觉活动中的作用是相当模糊的。为了了解成体神经发生在嗅觉功能中的意义，我们用他莫昔芬处理的Nestin-CreERT2；神经元特异性烯醇化咽毒素片段A(NSE-DTA)小鼠对新生神经元进行了基因消融。在这些小鼠中，他莫昔芬诱导的Cre重组酶允许NSE(Eno2)基因驱动分化神经元中DTA的表达，导致有效地消融前脑中新生的神经元。这些突变的小鼠能够像对照小鼠一样辨别气味。引人注目的是，尽管对照组和突变小鼠经常表现出对狐狸气味(一种捕食者气味)的冻结行为，但突变小鼠在条件作用下将气味与奖励联系在一起时接近这种气味，而对照组小鼠不接近这种气味。此外，尽管突变的雄性和雌性对其他性别的小鼠表现出正常的社会识别行为，但突变的雄性在雄雄之间的攻击性和对雌性的性行为方面存在缺陷，而突变的雌性在生育和哺育方面表现出缺陷，这表明已知依赖嗅觉的性别特异性活动受到了损害。这些结果表明，捕食者回避和嗅觉依赖和天生编程的性别特异性反应需要持续的神经发生。
Although the functional significance of adult neurogenesis in hippocampal-dependent learning and memory has been well documented, the role of such neurogenesis in olfactory activity is rather obscure. To understand the significance of adult neurogenesis in olfactory functions, we genetically ablated newly born neurons by using tamoxifen-treated Nestin-CreERT2; neuron-specific enolasediphtheria toxin fragment A (NSE-DTA) mice. In these mice, tamoxifen-inducible Cre recombinase allows the NSE (Eno2) gene to drive DTA expression in differentiating neurons, leading to the efficient ablation of newly born neurons in the forebrain. These mutant mice were capable of discriminating odors as competently as control mice. Strikingly, although control and mutant mice frequently showed freezing behaviors to a fox scent, a predator odor, mutant mice approached this odor when they were conditioned to associate the odor with a reward, whereas control mice did not approach the odor. Furthermore, although mutant males and females showed normal social recognition behaviors to other mice of a different sex, mutant males displayed deficits in male-male aggression and male sexual behaviors toward females, whereas mutant females displayed deficits in fertility and nurturing, indicating that sex-specific activities, which are known to depend on olfaction, are impaired. These results suggest that continuous neurogenesis is required for predator avoidance and sex-specific responses that are olfaction dependent and innately programmed.