|Memory > NMDAR Extinction in Dendritic Shaft|
NMDA receptors (NMDARs) are located not only at synapses, but also widely distributed in the extrasynaptic membrane. In particular, the spiny neurons of amygdala, striatum, and cerebral cortex are enriched with extrasynaptic NMDARs to produce NMDA plateaus that are crucial for the generation of action potentials. In the dentate gyrus (DG) of hippocampus, the extrasynaptic NMDARs also make significant contribution to neuronal firing, especially in young granule cells the action potential can be generated by NMDARs alone, without requiring AMPARs (Li et al., 2017). Hence, inhibition of NMDARs in the dendritic shaft can have significant impact on the activation of memory engram cells.
It has been well established that Ca2+ ions promote microtubule depolymerization (O'Brien et al., 1997; Lefèvre et al., 2011). Therefore, the elevated Ca2+ concentration accompanied with the NMDA plateau may cause microtubule depolymerization to produce free tubulin heterodimer, which may form the CABT complex with CRMP2, and consequently promoting NMDAR extinction. This provides a negative feedback to prevent excessive neuronal firing.
Author: Frank Lee