kaleidoscopik

Here’s a fine piece of work from Miwa et al. comparing the role of NR2B subunits in the lateral amygdala versus the CA1 region. NMDA receptors are glutamate receptors heavily implicated in the initiation of synaptic plasticity underlying learning and memory. They consist of NR1 subunits in complex with any of the subtypes of NR2 units (NR2A-NR2D). The story goes that NR2B subunits are prominent early in development but are replaced with NR2A subunits in adulthood. The “doogie mouse” was created by transgenically increasing the NR2B contribution in adult mice because NR2Bs allow a longer time window in which to initiate plasticity processes. SInce then, a story has emerged that NR2Bs are typically found outside the synapse and are only activated when the signal is so strong that glutamate spills over. Miwa et al take that apart by showing through electrophysiology and immunogold electron microscopy that NR2Bs are present in synapses in the LA and CA1. They then run down a whole list of differences between the two regions.

“The properties of NMDA receptors in the LA were distinct from those in the CA1 region: a greater contribution of the NR2B subunit to synaptic NMDA responses ; a higher NR2B/NR2A ratio and a higher ratio of NMDA to AMPA receptor-mediated synaptic transmission ; smaller synaptic currents in the I–V curve of NMDA receptors; and lower Mg2+ sensitivity.”

Ignoring all caveats for a minute, the amygdala is where fear memories are made and the hippocampus is where memories of space, context, and personal events are made. It’s interesting to consider how the different memory systems will respond to drugs that affect NMDA receptors and perhaps disorders such as epilepsy and schizophrenia that are sometimes associated with NMDA receptor malfunctions.
Functional contributions of synaptically localized NR2B subunits of the NMDA receptor to synaptic transmission and long-term potentiation in the adult mouse CNS
Hideki Miwa, Masahiro Fukaya, Ayako M. Watabe, Masahiko Watanabe and Toshiya Manabe