Regulation of PSD phosphorylation and protein interactions networks by LTP

在长时程增强（LTP）过程中，通过突触活动模式激活NMDAR被认为是 调节许多蛋白激酶，这些蛋白激酶通过磷酸化细胞内的蛋白质来增强突触传递。 突触后密度（PSD）。在兴奋性突触的PSD，这些磷酸化的蛋白质 被认为在蛋白质相互作用网络中相互关联。这些网络可以传达重要的机制， 在健康和疾病状态下在突触处处理、整合和存储信息。但只有 已知少量磷酸化位点。此外，没有关于NMDAR如何 依赖性高频刺激-LTP调节时间健康中的蛋白磷酸化网络， 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 LTP的诱导触发，并确定如何在β-肾上腺素能神经元的存在下， 受体激动剂调节PSD中的突触活动和蛋白质相互作用的模式， 和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CA 1迷你切片，质谱， 生物信息学和小鼠遗传学。这将有助于更好地了解SynGAP突变的作用。 LTP中PSD网络的组成和NMDAR与β-肾上腺素能受体的会聚 信号网络，并将告知未来的研究，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.