An analysis of morphological changes in visual cortical neurons after knocking down scaffolding proteins of glutamate receptors

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2008.Includes bibliographical references (leaf 17).NMDA receptor subunit changes have an important implication in synaptic development, learning, memory, and neuronal disorders. Previous studies have suggested that two membrane-associated guanylate kinase (MAGUK) family scaffolding proteins, SAP102 and PSD-95, are involved in the switch from predominance of NMDA receptors rich in NR2B subunits to that of NMDA receptors rich in NR2A subunits. Normally, eye opening causes PSD-95 levels to increase at synapses and its interactions with NR2A to increase while its interactions with NR2B decrease. In order to identify the exact roles of the two MAGUKs, this study examined changes in dendritic morphology of mouse visual cortical neurons at postnatal day 15 induced by eye opening and knocking down each of the two MAGUKs with small inhibitory RNAs (siRNAs). The changes I found include smaller cell bodies, increased frequency of dendritic branching, and a decrease in the number of dendritic intersections with a radial sphere centered on the cell body. Since dendritic patterning is critical for neuronal information processing, these results suggest an important aspect of MAGUK functions in cortical development. Further studies including mice at different ages and mice with closed eyes will determine the roles of MAGUKs in age- and activity-dependent development of the visual cortical circuit.by Connie M. Yee.S.B