rease the gene's ability to make the protein in the adult brain. This was then injected into fertilized mouse eggs where it was incorporated into the chromosomes of the mice. Tsien then set out to prove the theory that overexpression of NR2B in the brains of mice, leads to enhanced activation of NMDA receptors, which in turn leads to superior ability in learning and memory.
The NMDA receptors consist of NR1 subunits and various NR2 subunits. The NR1 subunit is needed for channel function and the NR2 subunit regulates channel gating and Mg2+ dependency. In the brain regions of the hippocampus and cortex the NR2A and NR2B subunits are the only subunits able to form the receptor complex with an NR1 subunit. Meaning, it has to be either NR2B or NR2A that could be responsible for extended channel opening. Tsien and his team examined the recombinant NR1-NR2B complex and found that it had a "longer excitatory postsynaptic potential (EPSPs) than the NR1-NR2A complex (Ya-Ping 1999)." Meaning that if the NR2B subunit is increased it should allow the NMDA receptors to increase the time the receptor channel is open. NR2B expression is downregulated during the transition from juvenile to adult stages, this corresponds with the gradual shortening of the EPSP duration of the NMDA channel. This can "decrease NMDA-mediated plasticity and maybe lead to the explanation of decreased memory performance in adult animals (Ya-Ping 1999)." "Hebbs Rule states that learning and memory are based on modifications of synaptic strength among neurons that are simultaneously active (Ya-Ping 1999)." In other words, "a synapse between cell A and cell B will be strengthened if the two cells are active at the same time (Gordon 2000)." To test whether the NR2B subunit is important for implicating Hebbs Rule and gating synaptic plasticity and memory; Tsien increased the NR2B subunit in the forebrain of the mouse usi...