Gliotransmitter
Gliotransmitters are chemicals released by glial cells to help neurons talk to each other. They are often linked to calcium (Ca2+) signaling inside glial cells, but new research questions how essential Ca2+ is for gliotransmission and how important glial signaling really is in the brain. The release of gliotransmitters mostly comes from astrocytes, a star-shaped type of glial cell that touches thousands of synapses through its many extensions and gap junctions. Because astrocytes connect to so many neurons, they can influence brain activity in many areas and in both directions.
Glial signaling is not limited to the brain’s gray matter. It also occurs at motor nerve endings with Schwann cells in the peripheral nervous system and between glial cells in the retina (Müller cells) and retinal neurons. The term glia comes from a Greek word meaning “glue,” reflecting an old idea that glial cells were passive supporters. We now know glia can be active players in neural communication. Although glial cells do not generate action potentials like neurons, they can become excitable, with Ca2+ changes that trigger gliotransmitter release and affect nearby neurons.
Ca2+ signals in astrocytes can influence currents in neighboring neurons, such as those activating NMDA receptors, which are involved in synaptic plasticity. Because glia outnumber neurons in the brain (glia make up more than 70% of brain cells), gliotransmitters released by astrocytes have the potential to shape brain signaling broadly. Glial cells also communicate with each other, with neurons, and with microglia, using inputs, information processing, and chemical signaling. Astrocyte Ca2+ signals can even help regulate brain blood flow.
The major gliotransmitters released from astrocytes are glutamate and ATP. Glutamate is the main excitatory neurotransmitter in the brain and can act on several receptors, including NMDA receptors, which are important for synaptic strengthening and learning. Glutamate release from astrocytes can synchronize neuronal activity and boost postsynaptic responses, influencing how often neurons fire.
ATP, another important gliotransmitter, can dampen neuronal activity by acting on purinergic receptors and adenosine receptors. ATP also helps insert AMPA receptors into synapses and can trigger calcium waves in astrocytes, spreading signals to nearby cells. In the retina, ATP can be converted to adenosine to hyperpolarize and calm neurons. ATP also plays a role in inflammation and remyelination after injury, entering the extracellular space to activate receptors on other cells. How exactly astrocytes release ATP is not fully understood, but Ca2+ and SNARE proteins are involved, with multiple release pathways likely contributing, including exocytosis.
Gliotransmission is not limited to astrocytes and neurons. It can occur between astrocytes, neurons, and microglia, and calcium waves can travel between astrocytes that are not in direct contact. The common idea of a tripartite synapse describes a synapse involving the presynaptic terminal, the postsynaptic neuron, and an astrocyte that modulates transmission. Depending on the gliotransmitter released, astrocytes can either enhance or inhibit neuronal signaling.
Disruptions in gliotransmission have been linked to various brain conditions. Some evidence points to a role in epilepsy (where excessive excitation may occur) and schizophrenia (where reduced gliotransmission or altered NMDA receptor activity may be involved). Depression has been associated with fewer astrocytes in the brain. In neurodegenerative diseases like Alzheimer's, there is increased glial activation and changes in gliotransmitter levels, including inflammatory molecules such as TNF, which may affect synaptic function.
Overall, gliotransmitters help glial cells participate in brain signaling, plasticity, and responses to injury, highlighting that glia are active players in neural communication, not just support cells.
This page was last edited on 2 February 2026, at 08:33 (CET).