Glutamate: What It Is & Function

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Glutamate is the most abundant excitatory neurotransmitter released by nerve cells in your brain. It plays a major role in learning and memory. For your brain to function properly, glutamate needs to be present in the right concentration in the right places at the right time. Too much glutamate is associated with such diseases as Parkinson’s disease, Alzheimer’s disease and Huntington’s disease.

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Glutamate is a neurotransmitter. Neurotransmitters are “chemical messengers.” Their job is to send messages between nerve cells (neurons) in your brain.

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Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

In your brain, glutamate is the most abundant excitatory neurotransmitter. An excitatory neurotransmitter excites or stimulates a nerve cell, making it more likely that the chemical message will continue to move from nerve cell to nerve cell and not be stopped. Glutamate is essential for proper brain function.

Glutamate is recycled and made by glial cells in your brain. Glial cells convert “used” glutamate to glutamine, which is converted back again into glutamate when delivered back to the terminal area of nerve cells.

Glutamate is also needed for making another neurotransmitter in your brain called gamma-aminobutyric acid (GABA). GABA is known as the “calming” neurotransmitter. It’s involved in sleep, relaxation, anxiety regulation and muscle function.

Glutamate is also an amino acid. Amino acids are the building blocks of protein. Glutamate is your body’s most abundant amino acid. Glutamate in your body is made and stored in muscle tissue.

Glutamate is perhaps best known as the food additive monosodium glutamate (MSG).

Neurotransmitters, like glutamate, are made by nerve cells and are stored in thin-walled vesicles called synaptic vesicles located at the axon terminal, which is at the end of each nerve cell. Each vesicle can contain thousands of neurotransmitter molecules.

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As a message or signal travels along a nerve cell, the electrical charge of the signal causes the vesicles of neurotransmitters — in this case, glutamate — to be released into a fluid-filled space that’s between nerve cells. This space is called a synapse. On the other side of the synapse is the next nerve cell. Glutamate must bind to specific message-receiving receptors on this next nerve cell. After binding, glutamate then triggers a change or action in this next nerve cell and the communication signal continues on its way from nerve cell to nerve cell.

Unlike other neurotransmitters, glutamate can bind to four different receptors (like a master key that can fit into and work four different partner locks). This allows glutamate to have a major presence and ability to stimulate and communicate with other nerve cells. Glutamate is involved in more than 90% of all excitatory functions in the human brain.

In your brain, groups of nerve cells connect to form smaller circuits (to manage smaller tasks like memory retrieval) or larger, more extensive networks (to carry out larger more complex tasks, such as sight, hearing or movement). Glutamate is the most abundant neurotransmitter that carries the chemical message across these circuits and networks. How glutamate acts at the synapse between nerve cells can either strengthen or weaken the communication signal between these cells, which then affects the function to be carried out. Less than the right amount of glutamate released at the right places for the right amount of time results in poor communication. Too much glutamate can damage nerve cells and the communication network.

Glutamate’s functions include:

• Learning and memory. By interacting with four different receptors, glutamate has more opportunities to continue to have messages successfully and quickly sent between nerve cells. This fast signaling and information processing is an important aspect of learning and memory. Glutamate also allows nerve cells to build associated information, which is a foundation of memory.
• Energy source for brain cells. Glutamate can be used as an energy source when glucose levels — the main source of energy — are low.
• Chemical messenger. Glutamate allows chemical messages to be sent between nerve cells.
• Sleep-wake cycle manager. According to animal studies, glutamate levels are high when you’re awake and during the rapid eye movement (REM) phase of sleep.
• Pain signaler. Higher levels of glutamate are associated with an increase in pain levels.

Ways that too much glutamate can be in your brain include:

• Too much glutamate is released by nerve cells.
• Glutamate, directly released from glial cells in your brain, adds to the total amount in your brain.
• Excess glutamate remains in the space between nerve cells (the synapse), which can lead to too many glutamate receptors being continuously activated and nerve cells being continuously excited.
• Nerve cell receptors have become oversensitive to glutamate, meaning that fewer glutamate molecules are needed to excite them.

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Too much glutamate in the brain can cause nerve cells to become overexcited. Overexcitement can lead to brain cell damage and/or death. In this case, glutamate is called an excitotoxin.

Having too much glutamate in the brain is associated with some conditions, including:

• Amyotrophic lateral sclerosis (Lou Gehrig’s disease).
• Multiple sclerosis.
• Alzheimer’s disease.
• Parkinson’s disease.
• Huntington’s disease.
• Stroke.
• Fibromyalgia.
• Chronic fatigue syndrome.

Mental health conditions that are thought to happen from problems with making or using glutamate include:

Too little glutamate in the brain is thought to result in:

• Trouble concentrating.
• Mental exhaustion.
• Insomnia.
• Low energy.

Glutamate is the most abundant excitatory neurotransmitter in your brain and central nervous system. It’s needed to keep your brain functioning properly. Glutamate plays a major role in shaping learning and memory. Glutamate needs to be present at the right concentrations in the right places at the right time. Too much glutamate in your brain, in the wrong place, in too high of a concentration and for too long can cause brain cell damage or death. Some neurodegenerative diseases associated with having too much glutamate exciting nerve cells include Parkinson’s disease, Alzheimer’s disease and Huntington’s disease. Problems in making or using glutamate have been linked to mental health disorders including autism, depression and schizophrenia.

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Cleveland Clinic’s health articles are based on evidence-backed information and review by medical professionals to ensure accuracy, reliability and up-to-date clinical standards.

Cleveland Clinic’s health articles are based on evidence-backed information and review by medical professionals to ensure accuracy, reliability and up-to-date clinical standards.

• Dana Foundation. Protecting the Brain from a Glutamate Storm. (https://www.dana.org/article/protecting-the-brain-from-a-glutamate-storm/) Accessed 4/25/2022.
• Institute of Medicine (US) Forum on Neuroscience and Nervous System Disorders. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary. (https://www.ncbi.nlm.nih.gov/books/NBK62187/) Washington (DC): National Academies Press (US); 2011. 2, Overview of the Glutamatergic System. Accessed 4/25/2022
• Peng S, Zhang Y, Zhang J, et al. Glutamate receptors and signal transduction in learning and memory. (https://pubmed.ncbi.nlm.nih.gov/20364330/) Mol Biol Rep 2011 Jan;38(1):453-60. Accessed 4/25/2022
• Stallard CN, Anoruo MD, Saadabadi A. Biochemistry, Glutamate (https://www.ncbi.nlm.nih.gov/books/NBK537267/). [Updated 2021 Jan 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Accessed 4/25/2022
• Watson CJ, Lydic R, Badhdoyan HA. Sleep duration varies as a function of glutamate and GABA in rat pontine reticular formation (https://pubmed.ncbi.nlm.nih.gov/21679185/). J Neurochem 2011 Aug;118(4):157-80. Accessed 4/25/2022
• Zhou Y, Danbolt NC. Glutamate as a neurotransmitter in the healthy brain (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133642/). J Neural Transm (Vienna). 2014;121(8):799-817. Accessed 4/25/2022.

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