Department of Neuroscience, Canadian Centre for Behavioural Neuroscience, The University of Lethbridge, Lethbridge, AB, T1K 3M4, Canada.
Hippocampus. 2013 Oct;23(10):890-902. doi: 10.1002/hipo.22146. Epub 2013 Jul 5.
Homer1a (H1a) is an immediate early gene involved in multiple forms of synaptic plasticity. It exhibits a postnatal increase in the rat forebrain (Brakeman et al. (1997) Nature 386:284-288) and reduces the density and size of dendritic spines in hippocampal neurons (Sala et al. (2003) J Neurosci 23:6327-6337). We evaluated hippocampal H1a expression at different postnatal ages (P3, P5, P7, P9, P15, P19, P23, P35, and adult) using Fluorescence In Situ Hybridization (FISH) and qRT-PCR. Maximal electroconvulsive shock (MECS) was used to induce maximal expression relative to home cage (HC) controls. Large scale images and confocal z-stacks from dorsal subiculum (DS), CA1, CA3, and dentate gyrus (DG) were analyzed by both manual and automated methods. In DS, CA1, and CA3 a significant proportion of cells (40%) expressed small but detectable levels of H1a from P3; however, MECS did not up-regulate H1a during the first postnatal week. MECS induced H1a positive cells during the second postnatal week and induction reached adult levels at P9. H1a-Intra Nuclear Foci (INF) size and intensity varied with age, increasing at P19-23 in CA1 and CA3 and from P9 to P23 in DS. In DG, H1a expression exhibited a lamination pattern and an H1a-INF size and intensity gradient across the granule cell layer, consistent with the outside-in maturation of DG granule cells. The developmental progression of H1a corresponds to the synaptic refinement period supporting the conclusion that H1a could play an important role in this process.
Homer1a（H1a）是一种参与多种形式突触可塑性的早期基因。它在大鼠前脑中表现出出生后的增加（Brakeman 等人，（1997）自然 386:284-288），并减少海马神经元树突棘的密度和大小（Sala 等人，（2003）神经科学 23:6327-6337）。我们使用荧光原位杂交（FISH）和 qRT-PCR 评估了不同出生后年龄（P3、P5、P7、P9、P15、P19、P23、P35 和成年）的海马 H1a 表达。最大电惊厥（MECS）用于诱导相对于家庭笼（HC）对照的最大表达。来自背侧下托（DS）、CA1、CA3 和齿状回（DG）的大比例尺图像和共聚焦 z 堆栈通过手动和自动方法进行分析。在 DS、CA1 和 CA3 中，从 P3 开始，相当一部分细胞（40%）表达小但可检测水平的 H1a；然而，MECS 在出生后的第一周内并没有上调 H1a。MECS 在出生后的第二周诱导 H1a 阳性细胞，诱导在 P9 达到成年水平。H1a-核内焦点（INF）的大小和强度随年龄而变化，在 CA1 和 CA3 中从 P19-23 增加，在 DS 中从 P9 到 P23 增加。在 DG 中，H1a 表达表现出分层模式和颗粒细胞层的 H1a-INF 大小和强度梯度，与 DG 颗粒细胞的外向成熟一致。H1a 的发育进展与突触细化期相对应，支持 H1a 可能在该过程中发挥重要作用的结论。
