Glutamate as a neurotransmitter in the healthy brain

Summary & key facts

Glutamate is the brain’s most common free amino acid and the main chemical that makes nerve cells fire. Scientists were surprised to find that it not only excites cells but can also over‑excite them until they die, a process called excitotoxicity. The brain keeps glutamate under control with strong uptake systems that remove it quickly and with the blood‑brain barrier that blocks glutamate from the blood. This paper reviews how glutamate works in a healthy brain, how it is stored and released, and how cells recycle it in the glutamate–glutamine cycle.

Key facts:

• Glutamate is the most abundant free amino acid in the brain and is the main excitatory chemical messenger that makes nerve cells activate.
• Glutamate can cause 'excitotoxicity', which means it can over‑excite nerve cells so much that they die.
• Glutamate acts through specific receptors on the surface of brain cells; those receptors are what let glutamate excite cells.
• The brain uses powerful uptake systems called glutamate transporters to keep the amount of glutamate outside cells low and to avoid excessive receptor activation.
• The blood‑brain barrier helps protect the brain by keeping most glutamate in the blood from entering the brain.
• Most of the glutamate used for signaling is packed into tiny membrane packets called synaptic vesicles at nerve endings and is released when those packets fuse with the nerve cell membrane.

Abstract

Glutamate is the most abundant free amino acid in the brain and is at the crossroad between multiple metabolic pathways. Considering this, it was a surprise to discover that glutamate has excitatory effects on nerve cells, and that it can excite cells to their death in a process now referred to as "excitotoxicity". This effect is due to glutamate receptors present on the surface of brain cells. Powerful uptake systems (glutamate transporters) prevent excessive activation of these receptors by continuously removing glutamate from the extracellular fluid in the brain. Further, the blood-brain barrier shields the brain from glutamate in the blood. The highest concentrations of glutamate are found in synaptic vesicles in nerve terminals from where it can be released by exocytosis. In fact, glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. It took, however, a long time to realize that. The present review provides a brief historical description, gives a short overview of glutamate as a transmitter in the healthy brain, and comments on the so-called glutamate-glutamine cycle. The glutamate transporters responsible for the glutamate removal are described in some detail.

Topics

Memory and Neural Mechanisms Neuroscience and Neuropharmacology Research Photoreceptor and optogenetics research

Categories

Cellular and Molecular Neuroscience Life Sciences Neuroscience

Tags

Central nervous system Dopamine Glutamate receptor Internal medicine Medicine Neurology Neuroscience Neurotransmitter Neurotransmitter Agents Neurotransmitter systems Psychology Receptor