Synapse-Associated Protein 102/dlgh3 Couples the NMDA Receptor to Specific Plasticity Pathways and Learning Strategies

• DOI: 10.1523/jneurosci.4457-06.2007
• Publication Date: 2007-03-07T17:16:22Z
• Authors: Peter C. Cuthbert; Lianne E. Stanford; Marcelo P. Coba; James A. Ainge; Ann E. Fink; Patricio Opazo; Jary Y. Delgado; Noboru H. Komiyama; Thomas J. O'Dell; Seth G. N. Grant
• Keywords: Guanylate kinase; Postsynaptic density

Understanding the mechanisms whereby information encoded within patterns of action potentials is deciphered by neurons central to cognitive psychology. The multiprotein complexes formed NMDA receptors linked synaptic membrane-associated guanylate kinase (MAGUK) proteins including synapse-associated protein 102 (SAP102) and other associated are instrumental in these processes. Although humans with mutations SAP102 show mental retardation, physiological biochemical involved unknown. Using knock-out mice, we found specific impairments plasticity induced selective frequencies stimulation that also required extracellular signal-regulated signaling. This was paralleled inflexibility impairment spatial learning. Improvement learning performance occurred extra training despite continued use a suboptimal search strategy, and, separate nonspatial task, mutants again deployed different strategy. Double-mutant analysis postsynaptic density-95 indicate overlapping functions two MAGUKs. These vivo data support model MAGUK couple receptor distinct downstream signaling pathways. provides mechanism for discriminating activity lead long-lasting changes strength as well aspects cognition mammalian nervous system.