Molecular mechanisms of AMPA receptor synapse formation

脑细胞(神经元)通过中枢神经系统传递电信息，并通过称为突触的特殊连接引发特定行为。在发育过程中，形成了复杂而精确的神经元突触连接模式。该项目的目标是了解在首席研究员实验室中发现的一种新蛋白(SynDIG1)在突触发育中发挥作用的机制。这项研究将验证SynDIG1通过与支架蛋白相互作用将AMPA型谷氨酸受体(AMPA-Rs)锚定在突触后脑室的假设。研究人员将使用包括生物化学、免疫细胞化学和电生理学在内的多种方法来解决这种可能性。虽然突触前分化领域已经取得了重大进展，如突触小泡聚集和突触后支架和NMDA型谷氨酸受体(NMDA型谷氨酸受体)的招募，但关于突触发育过程中AMPA-R招募的分子知之甚少。因此，拟议的实验结果将填补突触发育和功能领域的一个重大空白。拟议研究的更广泛影响包括将国际和平研究所的研究和教育活动结合起来，特别是在扩大来自代表不足群体(主要是西班牙裔/拉丁裔)的本科生参与的背景下。国际学生联合会积极参与了各种旨在增加攻读理科研究生学位的人数不足的学生的校园计划；因此，国际学生联合会处于有利地位，可以将这些学生招募到实验室作为该项目研究小组的成员。本科生的参与将由PI与实验室的研究生一起指导，从而整合研究、教学和科学界为在实验室攻读研究生的学生而开展的外展活动。

Brain cells (neurons) transmit electrical information through the central nervous system and elicit specific behaviors through specialized connections called synapses. During development, the intricate and precise pattern of neuronal synapse connections is formed. The goal of this project is to understand the mechanism by which a novel protein (SynDIG1) that was identified in the Principal Investigator's (PI) laboratory functions in synapse development. This study will test the hypothesis that SynDIG1 anchors AMPA-type glutamate receptors (AMPA-Rs) at the postsynaptic compartment via interaction with scaffolding proteins. The researchers will use a combination of approaches including biochemistry, immunocytochemistry, and electrophysiology to address this possibility. While significant progress has been made in the field regarding presynaptic differentiation such as synaptic vesicle clustering and postsynaptic recruitment of scaffolds and NMDA-type glutamate receptors (NMDA-Rs), less is known about the molecules implicated in AMPA-R recruitment during synapse development. Thus, the results of the proposed experiments will fill a major gap in the field of synapse development and function. The broader impacts of the proposed studies include integration of the research and education activities of the PI, specifically in the context of broadening the participation of undergraduate students from underrepresented groups (primarily Hispanic/Latino). The PI is an active participant in various campus programs aimed to increase the number of underrepresented students pursuing postgraduate degrees in science; thus, the PI is in a strong position to recruit such students to the laboratory as members of the research team for this project. Undergraduate participation will be directed by the PI in conjunction with graduate students in the laboratory, thereby integrating research, teaching, and scientific community outreach activities for students pursuing graduate studies in the laboratory.