NMDA glutamate receptors function as receptors which bond with glutamates, and are known to be deeply involved in memory and learning. In order for memories to be created inside the brain, these NMDA glutamate receptors must first be transported to the synapses. Now, a study from researchers at the University of Tsukuba and the University of Tokyo clarifies the mechanism in the brain which prevents derailment of this receptor transportation system which supports memory. The team state their findings show that a molecule, known as the microtubule-associated protein 1A (MAP1A), connects NMDA glutamate receptors to microtubules as they are being transported to the synapses, stabilizing the receptors and preventing them from becoming derailed, as well as playing a crucial role in improving the overall efficiency and stability of the transportation process.
Previous studies show that MAP1A is a member of the major non-motor microtubule-binding proteins. It has been suggested that MAP1A tethers NMDA receptors to the cytoskeleton by binding with proteins PSD-93 and PSD-95, although the function of MAP1A remains elusive. The current study shows that in a mice, MAP1A plays an essential role in maintaining synaptic plasticity through an analysis of a MAP1A knock-out mouse model.
The current study utilises newly generated mutant mice lacking MAP1A to show mice lacking this protein exhibit learning disabilities, and reduced synaptic plasticity attributable to disruptions of the anchoring machinery. Results show in the nerve cells of mice which lack MAP1A, the NMDA glutamate receptors are not carried effectively to the synapses, resulting in a remarkable loss of memory-based capabilities in the mice.
Data findings show that the mice exhibited learning disabilities, which correlated with decreased long-term potentiation and long-term depression in the hippocampal neurons, as well as a reduction in the extent of NMDA receptor-dependent excitatory postsynaptic potential. Results show that enhanced activity-dependent degradation of PSD-93 and reduced transport of NMDA receptors in dendrites is likely responsible for altered receptor function in neurons lacking MAP1A. The lab conclude these data suggest that tethering of NMDA receptors with the cytoskeleton through MAP1A is fundamental for synaptic function.
The team surmise that their work is the first to report the significance of non-motor microtubule-associated protein in maintaining synaptic plasticity. They go on to add that this is done through a novel mechanism, namely, anchoring of NMDA receptors to cytoskeleton supporting their transport to stabilize postsynaptic density scaffolds binding to NMDA receptors. For the future, the researchers state that discoveries such as receptor transport abnormalities in the brains of schizophrenia patients, have started to show the receptors’ deep involvement in neuropsychiatric disorders. They conclude that the development of drug and gene therapies which can be effective on the receptor transport support system clarified in this study are expected to give rise to new treatment strategies for memory impairment and schizophrenia.
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An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.