Journal
JOURNAL OF NEUROSCIENCE
Volume 35, Issue 47, Pages 15539-15554Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2671-15.2015
Keywords
learning and memory; microtubule-associated protein; neuronal plasticity; NMDA receptor; transport
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Japan Agency for Medical Research and Development
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Microtubule-associated protein 1A (MAP1A) is a member of the major non-motor microtubule-binding proteins. It has been suggested that MAP1A tethers NMDA receptors (NRs) to the cytoskeleton by binding with proteins postsynaptic density (PSD)-93 and PSD-95, although the function of MAP1A in vivo remains elusive. The present study demonstrates that mouse MAP1A plays an essential role in maintaining synaptic plasticity through an analysis of MAP1A knock-out mice. The mice exhibited learning disabilities, which correlated with decreased long-term potentiation and long-term depression in the hippocampal neurons, as well as a concomitant reduction in the extent of NR-dependent EPSCs. Surface expression of NR2A and NR2B subunits also decreased. Enhanced activity-dependent degradation of PSD-93 and reduced transport of NR2A/2B in dendrites was likely responsible for altered receptor function in neurons lacking MAP1A. These data suggest that tethering of NR2A/2B with the cytoskeleton through MAP1A is fundamental for synaptic function.
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