CAREER: Molecular Regulation of Cortical Synapse Development

正常的大脑发育需要精心构建一个包含数十亿神经元的网络。 这个复杂的过程需要这些细胞之间数万亿个突触连接的精确启动和随后的成熟。 本研究项目旨在提高我们对调控皮层突触结构和功能发育成熟的细胞和分子机制的理解。这些研究集中在一个独特的神经递质受体，N-甲基-D-天冬氨酸（NMDA）受体的作用。 已知NMDA受体可以感知从其他神经元释放的谷氨酸，它可以调节突触强度的变化，而突触强度是成年人大脑学习和记忆的基础。 然而，这些受体在突触发育过程中的作用还不太清楚。 有趣的是，这些受体的蛋白质亚基组成在发育过程中受到严格控制。 NMDA受体是由两个NR 1和两个NR 2亚基缔合形成的异多聚体结构。 在胚胎发育晚期和出生后早期，突触发生的增加与NR 2B亚基的独家表达和结合到该受体复合物相对应。 这些研究应用遗传学、分子生物学和电生理学的现有技术来探测这些独特的含NR 2B受体在出生后皮质回路图案形成过程中的作用。为本科生和研究生提供导师支持。 此外，该项目旨在通过启动神经生物学研究年度培训课程，促进路易斯安那州少数民族学校学生在神经科学和/或生物医学研究方面的就业机会。 该课程将于每年春季在路易斯安那州Cocodrie的路易斯安那大学海洋联盟（LUMCON）DeFelice海洋站举行。

Proper brain development involves elaboration of a network containing billions of neurons. This complex process requires the precise initiation, and subsequent maturation, of trillions of synaptic connections between these cells. This research project aims to improve our understanding of the cellular and molecular mechanisms that regulate the developmental maturation of cortical synapse structure and function. These studies focus on the role of a unique neurotransmitter receptor, the n-methyl-d-aspartate (NMDA) receptor. NMDA receptors, which sense glutamate released from other neurons are known to regulate changes in synaptic strength that underlie learning and memory in the adult brain. However, the role of these receptors during synapse development is less well understood. Interestingly, the protein subunit composition of these receptors is tightly controlled during development. NMDA receptors are heteromultimeric structures formed by association of two NR1 and two NR2 subunits. Heightened synaptogenesis, during late embryogenesis and early postnatal life, corresponds with the exclusive expression and incorporation of NR2B subunits to this receptor complex. These studies apply current techniques in genetics, molecular biology and electrophysiology to probe the role of these unique NR2B-containing receptors during a postnatal cortical circuit patterning. Mentorship support is provided for both undergraduate and graduate students. In addition this project aims to promote career opportunities in neuroscience and/or biomedical research to students at minority-serving schools in Louisiana through the initiation of an annual training course in Neurobiology research. This course will be held each spring at the Louisiana Universities Marine Consortium (LUMCON) DeFelice Marine Station in Cocodrie Louisiana.