Glutamate is the primary excitatory neurotransmitter of the mammalian central nervous system. It exerts very powerful stimulating effects on neuronal activity. Glutamate is synthesized in the brain’s neuron terminals from both glucose and glutamine that is supplied by glial cells. Like other neurotransmitters, it is stored in presynaptic vesicles until needed for release across a synapse.
Glutamate and Central Nervous System (CNS)
The reason glutamate is the primary excitatory neurotransmitter of the CNS is because, when released, it increases the likelihood that the targeted postsynaptic neuron will fire an action potential, which will lead to more firing and communication throughout the nervous system.
Not only does it increase neuronal activity, it is also thought to play a key role in learning and thus memory formation. The glutamate receptor NMDA has become a major focus of attention in recent years because of its involvement in learning through making neuronal connections in the brain stronger. The term used for this in neuroscience is called long-term potentiation. In basic terms, when the NMDA receptor is activated by glutamate on a postsynaptic neuron, the next time that receptor is stimulated, it won’t need as much glutamate as before to fire an action potential down the postsynaptic neuron. The connection between the two neurons is now stronger and will fire more often because less glutamate is required. Thus, the formation of a memory occurs as the neuronal connection is remembered and will fire again more readily.
Excess Gluramatergic activity
Although glutamatergic neurotransmission via the NMDA receptor is important for learning and memory, excess firing can have unwanted side effects. Overly-excited NMDA receptors have been shown to have a pivotal role in:
- Drug Addiction
- Neurotoxic effects of brain ischemia/stroke
- Parkinson’s Disease
- Alzheimer’s dementia
- Hypoglycemia (1) (3) (4)
Both NMDA and AMPA (another major receptor of glutamate) receptor antagonists (that block glutamate from binding to receptors) have been shown to be powerfully neuroprotective in animal models of stroke, demonstrating the damaging effects of high glutamate levels (2).
Glutamate and Neurotransmitter Testing
We can see how adequate glutamatergic activity can be important for neurotransmission, learning, and memory, yet we can also see how excess glutamatergic activity can be neurotoxic and damaging to neuronal health. Thus, it is important to measure an individual’s level of glutamate in order to see if it is imbalanced. If the glutamate level is low, implementing l-glutamine supplementation can help restore it and potentially increase glutamatergic neurotransmission. If the glutamate level is high, implementing supplemental support for GABA can help lower it as GABA is a potent inhibitor of glutamate. Also, high glutamate can be caused by MSG and aspartame intake. If your glutamate level is high, you should avoid having these ingredients in your diet as they may elevate glutamate levels.
- Cooper JR, Bloom FE, Roth RH. The Biochemical Basis of Neuropharmacology. New York: Oxford University Press, 1996.
- Glutamate as a Neurotransmitter in the Brain: Review of Physiology and Pathology. Brian S. Meldrum. Journal of Nutrition. 2000;130:1007S-1015S
- Glutamatergic mechanisms in different disease states: overview and therapeutic implications- An introduction. Tzschentke TM, Grunenthal GmbH. Amino Acids 2002;23(1-3):147-52 40.
- Plasma levels of neuroexcitatory amino acids in patients with migraine or tension headache. Alam Z, et al. J Neurol Sci. 1998;156(1):102-6.