. A neuronal channel protein
which opens upon being bound by the amino acid glutamate
and having it's neuron multiply fired. Open NMDA receptor
s allow calcium ion
s to enter the neuron, potentiating
its action and making it more sensitive to stimulation
. This effect is is theorised to be responsible for associative memory
in the brain. It is therefore very
NMDA receptors are closed on inactive neurons. Use of some neurons causes glutamate to be released around them, letting nearby NMDA receptors become partially open, but still partially blocked by a magnesium ion. The partially open state allows potassium and sodium ions to enter or exit, depending on the firing state of the neuron. When a neuron is fired often enough with the NMDA receptors partially open, the magnesium ion dislodges from the Mg site, allowing calcium ions into the cell. Thus the neuron's action is most potentiated when both the glutamate-releasing neuron and another neuron act on it, in theory causing it to learn association between the two.
If the NDMA receptors are open too long, or too many are open, an excess of calcium ions can enter the neuron. The excess calcium activates enzymes, which eventually destroy the cell membrane, killing the cell. An excess of glutamate can be caused by the after effects of stroke, and also occurs in epilepsy, Huntington's Disease, and AIDS. This effect of this damage by overstimulation is referred to as exitotoxicity.
Interestingly, it appears that having more than a normal amount of NMDA receptors isn't harmful, and does not lead to excess calcium. In an experiment done at Princeton, the gene responsible for the NMDA receptors in mice (gene NR2B, FYI) was spliced into another area, causing it to be expressed at double the usual rate. The resulting mice were had more powerful and longer lasting neurological action potentials, resulting in better memory and generally higher intelligence. They scored better than regular mice at mazes and other aptitude tests, and didn't suffer from more seizures or a shorter lifespan than the control group of mice. These were the so-called Doogie mice you might have seen on the news a few years back.
NMDA receptors may also be blocked by chemicals such as ketamine, phencyclidine, and dextromethorphan. The receptors must be fully open (that is, bound by glutamate and stimulated to release the magnesium ion) for the chemical to enter. When it does, it binds to the PCP site on the inside of the NMDA receptor, and allows no further calcium ions -- or anything else -- to get through. If enough of the neuron's NMDA receptors are blocked, memories are unable to be formed using that neuron, and even if not, the neuron's function in memory is impaired. At low doses this effect is recreational (see: DXM), and in high doses is completely anesthetic. Normal NMDA activity controls release of acetylcholine and other neurotransmitters, so blockading it leads to overstimulation in some areas of the brain, and thence to Olney's lesions.
In situations of oxygen deprivation and low blood flow, a glutamate "flood" happens throughout the brain, even in areas not associated with cognition. It is theorized that there is a neurochemical that is also released in these situations which is a ligand for the PCP site on the NMDA receptor, and thus blocks the glutamate from entering the cell and causing exitotoxicity. In this role, NMDA blockade would protect more neurons from glutamate overstimulation than it would kill through acetylcholine overstimulation down the line. It is further thought that any extremely high level of stress, not just oxygen deprivation, may cause the glutamate flood and NMDA blockade. This could explain depersonalization-type effects such as near-death experiences, and also explains why many people find the dissociative experience to be (subjectively, of course) a lot like death.