Juvenile neurogenesis makes essential contributions to adult brain structure and plays a sex-dependent role in fear memories.
Juvenile neurogenesis makes essential contributions to adult brain structure and plays a sex-dependent role in fear memories.
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DOI：
10.3389/fnbeh.2012.00003
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发表时间：
2012
影响因子：
3
通讯作者：
Fanselow MS
中科院分区：
文献类型：
--
作者：
Cushman JD;Maldonado J;Kwon EE;Garcia AD;Fan G;Imura T;Sofroniew MV;Fanselow MS
在整个幼年发育过程中，出生后神经发生（PNN）为嗅球（OB）和齿状回（DG）提供神经元，但这种贡献的数量、数量、时间动态和功能作用尚未明确。通过使用转基因小鼠模型进行细胞谱系追踪和条件细胞消融，我们发现，在2周龄至2月龄期间，幼鼠神经发生逐渐增加颗粒神经元总数，OB增加约40%，DG增加25%，此后总数保持稳定。这些发现表明，绝大多数出生后这些区域的净神经元增加发生在幼年时期，而成年后的神经发生主要是在这两个区域的颗粒细胞的替换。在我们的条件细胞消融小鼠模型中的行为分析表明，在少年期和青年期PNN的完全丧失会产生一组特定的性别依赖的认知变化。我们观察到正常的海马体独立延迟恐惧条件反射，但恐惧过度泛化到新的听觉刺激，这与PNN在精神病理中的作用一致。标准情境恐惧条件反射完好无损，然而，暴露前依赖情境恐惧受损，这表明PNN在附带情境学习中的特定作用。两个高度相似的语境之间的语境歧视增强了；表明上下文模式分离增强或时间整合受损。我们还观察到对嗅觉线索的依赖减少，这与OB PNN在有效处理嗅觉信息中的作用是一致的。因此，在断奶、早期社会互动和性成熟等关键行为发育时期，幼年神经发生大大增加了OB和DG中的颗粒神经元总数，并在恐惧记忆中发挥性别依赖作用。
Postnatal neurogenesis (PNN) contributes neurons to olfactory bulb (OB) and dentate gyrus (DG) throughout juvenile development, but the quantitative amount, temporal dynamics and functional roles of this contribution have not been defined. By using transgenic mouse models for cell lineage tracing and conditional cell ablation, we found that juvenile neurogenesis gradually increased the total number of granule neurons by approximately 40% in OB, and by 25% in DG, between 2 weeks and 2 months of age, and that total numbers remained stable thereafter. These findings indicate that the overwhelming majority of net postnatal neuronal addition in these regions occurs during the juvenile period and that adult neurogenesis contributes primarily to replacement of granule cells in both regions. Behavioral analysis in our conditional cell ablation mouse model showed that complete loss of PNN throughout both the juvenile and young adult period produced a specific set of sex-dependent cognitive changes. We observed normal hippocampus-independent delay fear conditioning, but excessive generalization of fear to a novel auditory stimulus, which is consistent with a role for PNN in psychopathology. Standard contextual fear conditioning was intact, however, pre-exposure dependent contextual fear was impaired suggesting a specific role for PNN in incidental contextual learning. Contextual discrimination between two highly similar contexts was enhanced; suggesting either enhanced contextual pattern separation or impaired temporal integration. We also observed a reduced reliance on olfactory cues, consistent with a role for OB PNN in the efficient processing of olfactory information. Thus, juvenile neurogenesis adds substantively to the total numbers of granule neurons in OB and DG during periods of critical juvenile behavioral development, including weaning, early social interactions and sexual maturation, and plays a sex-dependent role in fear memories.
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影响因子：
1.7
作者：
Beesdo, Katja;Knappe, Susanne;Pine, Daniel S.
通讯作者：
Pine, Daniel S.
影响因子：
25
作者：
Imayoshi, Itaru;Sakamoto, Masayuki;Kageyama, Ryoichiro
通讯作者：
Kageyama, Ryoichiro
影响因子：
25
作者：
Denise, A;Garcia, R;Sofroniew, MV
通讯作者：
Sofroniew, MV
DOI：
10.1176/appi.ajp.2009.09030410
发表时间：
2010-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Lissek S;Rabin S;Heller RE;Lukenbaugh D;Geraci M;Pine DS;Grillon C
通讯作者：
Grillon C
影响因子：
56.9
作者：
BAYER, SA;YACKEL, JW;PURI, PS
通讯作者：
PURI, PS