A Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortex

• DOI: 10.1523/jneurosci.4585-12.2013
• Publication Date: 2013-05-08T16:38:10Z
• Authors: Akira Yoshii; Jian-Ping Zhao; Swarna Pandian; Brigitte van Zundert; Martha Constantin...
• Keywords: Axoplasmic transport; Silent synapse

Myosin Va (MyoVa) mediates F-actin-based vesicular transport toward the plasma membrane and is found at neuronal postsynaptic densities (PSDs), but role of MyoVa in synaptic development function largely unknown. Here, studies using dominant-negative neurological mutant mouse Flailer, we find that plays an essential activity-dependent delivery PSD-95 other critical PSD molecules to synapses endocytosis AMPA-type glutamate receptors (AMPAR) dendrites CNS neurons. known carry a complex containing major scaffolding proteins mature PSD, PSD-95, SAPAP1/GKAP, Shank, Homer dendritic spine synapses. In neurons show abnormal shaft localization stargazin, dynamin3, AMPARs morphology. Flailer also have abnormally high AMPAR miniature current frequencies spontaneous currents are more frequent larger than wild-type while numbers NMDAR remain normal. The abnormalities consistent with severely disrupted developmental regulation long-term depression cortical Thus fundamentally important both localizing spines organizing synapse for normal function. For this reason mice will be valuable further dissecting circuit refinement neuropsychiatric diseases where disruptions frequently observed.