Celikel Tansu, Marx Verena, Freudenberg Florian, Zivkovic Aleksandar, Resnik Evgeny, Hasan Mazahir T, Licznerski Pawel, Osten Pavel, Rozov Andrej, Seeburg Peter H, Schwarz Martin K
Department of Cell Physiology, Max-Planck Institute for Medical Research, Heidelberg Germany.
Front Neurosci. 2007 Oct 15;1(1):97-110. doi: 10.3389/neuro.01.1.1.007.2007. eCollection 2007 Nov.
Long Homer proteins forge assemblies of signaling components involved in glutamate receptor signaling in postsynaptic excitatory neurons, including those underlying synaptic transmission and plasticity. The short immediate-early gene (IEG) Homer1a can dynamically uncouple these physical associations by functional competition with long Homer isoforms. To examine the consequences of Homer1a-mediated "uncoupling" for synaptic plasticity and behavior, we generated forebrain-specific tetracycline (tet) controlled expression of Venus-tagged Homer1a (H1aV) in mice. We report that sustained overexpression of H1aV impaired spatial working but not reference memory. Most notably, a similar impairment was observed when H1aV expression was restricted to the dorsal hippocampus (HP), which identifies this structure as the principal cortical area for spatial working memory. Interestingly, H1aV overexpression also abolished maintenance of CA3-CA1 long-term potentiation (LTP). These impairments, generated by sustained high Homer1a levels, identify a requirement for long Homer forms in synaptic plasticity and temporal encoding of spatial memory.
长Homer蛋白在突触后兴奋性神经元中形成参与谷氨酸受体信号传导的信号成分组装体，包括那些构成突触传递和可塑性基础的成分。短的即早基因（IEG）Homer1a可通过与长Homer异构体的功能竞争动态地解开这些物理关联。为了研究Homer1a介导的“解偶联”对突触可塑性和行为的影响，我们在小鼠中生成了前脑特异性四环素（tet）控制的维纳斯标记的Homer1a（H1aV）表达。我们报告，H1aV的持续过表达损害了空间工作记忆，但不影响参考记忆。最值得注意的是，当H1aV表达局限于背侧海马体（HP）时，也观察到了类似的损害，这将该结构确定为空间工作记忆的主要皮质区域。有趣的是，H1aV过表达还消除了CA3-CA1长期增强（LTP）的维持。由持续高水平的Homer1a产生的这些损害表明，长Homer形式在突触可塑性和空间记忆的时间编码中是必需的。
