Regulation of PSD phosphorylation and protein interactions networks by LTP

长时程增强(LTP)过程中突触活动模式激活NMDAR被认为是 通过磷酸化体内的蛋白来调节一些加强突触传递的蛋白激酶 突触后密度(PSD)。在兴奋性谷氨酸能突触的PSD处，这些磷酸化蛋白 被认为与蛋白质相互作用网络有关。这些网络可以传递重要的机制 在健康和疾病状态下，在突触处处理、整合和存储信息。然而，只有一个 少量的磷酸化位点是已知的。此外，没有关于NMDAR如何 依赖高频刺激-LTP调制时间健康和时间健康的蛋白质磷酸化网络 疾病状态。 我们的主要目标是确定时间和NMDAR依赖的磷酸化网络 由长时程增强的诱导触发，并确定突触刺激在β-肾上腺素能 受体激动剂调节两种野生型PSD的突触活动和蛋白质相互作用的模式 以及SynGAP突变小鼠，一种智力残疾的小鼠模型。 为此，我们将使用小鼠海马区CA1小切片、质谱仪、 生物信息学和小鼠遗传学。这将使我们更好地理解SynGAP突变的作用 PSD网络的组成及NMDAR和β-肾上腺素能受体在长时程增强中的汇聚 并将为未来的研究提供信息，使其能够操纵和调节PSD信号。

The activation of NMDAR by patterns of synaptic activity during long-term potentiation (LTP) is thought to regulate a number of protein kinases that potentiate synaptic transmission by phosphorylating proteins within the postsynaptic density (PSD). At the PSD of excitatory glutamatergic synapse, these phosphorylated proteins are thought to associate in protein interaction networks. These networks can convey important mechanism for processing, integrating and storing information at synapses in health and disease states. However, only a small number of phosphorylation sites are known. Moreover, there is no information on how NMDAR dependent high frequency stimulation-LTP modulates protein phosphorylation networks in temporal health and disease states. Our primary objectives here are to determine the temporal and NMDAR dependent phosphorylation networks triggered by the induction of LTP, and identify how synaptic stimulation in the presence of β-adrenergic receptor agonists regulates patterns of synaptic activity and protein interactions in the PSD, of both wild type and SynGAP mutant mice, a mouse model of intellectual disability. For this purpose we will use a combination of mouse hippocampus CA1 mini-slices, mass spectrometry, bioinformatics and mouse genetics. This will allow a better understanding of the role of the SynGAP mutation in the composition of PSD networks and the convergence of NMDAR and β-adrenergic receptors in LTP signaling networks and will inform future studies to be able to manipulate and regulate PSD signaling.