The role of synaptopodin, the spine apparatus and the axonal cisternal organelle in activity-dependent synaptic and network plasticity in the dentate gyrus

学习和记忆的形成伴随着海马中突触强度（可塑性）的变化。突触足蛋白（Synaptopodin）是一种肌动蛋白相关蛋白，位于海马神经元树突棘的棘器（突触兴奋的靶点）和轴突起始段的脑池细胞器（GABA能突触抑制的靶点）。肌动蛋白细胞骨架及其相关蛋白（包括突触足蛋白）的活性依赖性变化在海马神经元的结构突触可塑性中起着至关重要的作用（Zhaazawa et al. 2003，Ouyang et al. 2005）。突触足蛋白缺陷型小鼠缺乏棘器和脑池细胞器（Deller等人，2003; Bas Orth等人，未出版）。我们计划研究短期可塑性，长期可塑性（LTP）和复发性抑制野生型和synaptopodin缺陷小鼠海马颗粒细胞刺激后，他们的主要传入输入（perforant-path），在体内和体外条件下。而受损的LTP可能与树突棘装置的缺乏，改变复发抑制可能与轴突起始段缺乏脑池细胞器。将使用脑池细胞器（突触足蛋白）、轴突起始段（α-IV-血影蛋白）以及GABA和GABAA受体的标记物对结构变化进行组织学研究。我们将使用一个计算模型来分析海马抑制和兴奋的平衡。我们的工作将导致更好地了解海马突触可塑性的结构变化。

Learning and memory formation are accompanied by changes of synaptic strength (plasticity) in the hippocampus. Synaptopodin is an actin-associated protein that is located at both the spine apparatuses of dendritic spines (targets of synaptic excitation) and the cisternal organelles of axon initial segments (targets of GABAergic synaptic inhibition) in hippocampal neurons. Activity-dependent changes in the actin cytoskeleton and its associated proteins, including synaptopodin, play a crucial role in structural synaptic plasticity in hippocampal neurons (Fukazawa et al. 2003, Ouyang et al. 2005). Synaptopodin-deficient mice lack spine apparatuses and cisternal organelles (Deller et al. 2003; Bas Orth et al., unpublished). We plan to study short-term plasticity, long-term plasticity (LTP) and recurrent inhibition in wildtype and synaptopodin-deficient mice on hippocampal granule cells following stimulation of their main afferent input (perforant-path), under in vivo and in vitro conditions. Whereas an impaired LTP may be associated with the lack of dendritic spine apparatuses, an altered recurrent inhibition might be related to the lack of cisternal organelles at axon initial segment. Structural changes will be studied histologically with markers for the cisternal organelle (synaptopodin), the axon initial segment (ß-IV-spectrin), and GABA and GABAA receptors. We will use a computational model to analyse the balance of hippocampal inhibition and excitation. Our work will lead to a better understanding of the structural changes underlying synaptic plasticity in the hippocampus.