Long-Term In Vivo Imaging of Dendritic Spines in the Hippocampus Reveals Structural Plasticity
Long-Term In Vivo Imaging of Dendritic Spines in the Hippocampus Reveals Structural Plasticity
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DOI：
10.1523/jneurosci.1464-14.2014
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发表时间：
2014-10-15
影响因子：
5.3
通讯作者：
Fuhrmann, Martin
中科院分区：
文献类型：
--
作者：
Gu, Ligang;Kleiber, Stefanie;Fuhrmann, Martin
海马功能对学习和记忆很重要。在记忆加工过程中，海马CA 1区神经元通过整合来自CA 3区和内嗅皮层的兴奋性突触输入起着至关重要的作用。这些神经元几乎只在树突棘上接受兴奋性输入。树突棘的形成和消除--结构可塑性--反映了海马网络内的布线变化。尽管海马在学习和记忆中的相关性，大多数关于结构可塑性的体内数据来自皮质区域。我们建立了一个慢性海马窗的方法，使用双光子显微镜可视化树突棘在所有CA 1海马层，并在数周的时间过程。此外，甚至在齿状回颗粒细胞可以可靠地检测。我们发现放射层中的棘密度（类似于每微米1.1）在数周内保持稳定。然而，一小部分（3.4%）的棘形成和消除成像会话之间，这表明CA 1神经元的棘在成年小鼠中表现出结构可塑性。此外，我们测试了海马窗植入可能的炎症或行为副作用。小鼠表现出短暂的小胶质细胞增生和星形胶质细胞增生增加，在几周内下降。我们没有发现任何差异的行为表现在一个开放的领域和上下文的恐惧条件反射范例。总之，海马长时程双光子成像揭示了CA 1区锥体神经元树突棘的结构可塑性。这种方法可能提供一个强大的工具来分析在健康和疾病的海马学习和记忆过程中神经元网络重新布线的变化。
Hippocampal function is important for learning and memory. During memory processing, hippocampal CA1 neurons play a crucial role by integrating excitatory synaptic input from CA3 and the entorhinal cortex. These neurons receive excitatory input almost exclusively on dendritic spines. The formation and elimination-structural plasticity-of dendritic spines reflect wiring changes within the hippocampal network. Despite the relevance of the hippocampus in learning and memory, most in vivo data on structural plasticity derive from cortical regions. We established a chronic hippocampal window approach using two-photon microscopy to visualize dendritic spines throughout all CA1 hippocampal layers and over a time course of weeks. Moreover, even granule cells in dentate gyrus could be reliably detected. We found that the spine density in stratum radiatum (similar to 1.1 per micrometer) remained stable over weeks. However, a small fraction (3.4%) of spines were formed and eliminated between imaging sessions, which demonstrated that spines of CA1 neurons exhibit structural plasticity in adult mice. In addition, we tested for possible inflammatory or behavioral side effects of hippocampal window implantation. Mice exhibited a transient increase in microgliosis and astrogliosis, which declined within a few weeks. We did not detect any difference in behavioral performance in an open-field and contextual fear-conditioning paradigm. In conclusion, hippocampal long-term two-photon imaging revealed structural plasticity of dendritic spines in CA1 pyramidal neurons. This approach may provide a powerful tool to analyze changes in neuronal network rewiring during hippocampal learning and memory processes in health and disease.