The word “glia,” German for “glue,” illustrates the original belief among scientists that these cells play a passive role in neural signaling, being responsible only for neuronal structure and support within the brain.  Glial cells cannot produce action potentials and therefore were not suspected as playing an important and active communicative role in the central nervous system, because synaptic transmission between neurons is initiated with an action potential. However, research shows that these cells express excitability with changes in the intracellular concentrations of Ca2+. Gliotransmission occurs because of the ability of glial cells to induce excitability with variations in Ca2+ concentrations. Changes in the concentration of Ca2+ correlate with currents from NMDA receptor-mediated neurons which are measured in neighboring neurons of the ventrobasal (VB) thalamus.  Because glial cells greatly outnumber neurons in the brain, accounting for over 70% of all cells in the central nervous system, gliotransmitters released by astrocytes have the potential to be very influential and important within the central nervous system, as well as within other neural systems throughout the body.  These cells do not simply carry functions of structural support, but can also take part in cell-to-cell communication with neurons, microglia, and other astrocytes by receiving inputs, organizing information, and sending out chemical signals.  The Ca2+ signal from the astrocyte may also participate in controlling blood flow in the brain. 
Gliotransmitters have been shown to control synapse development and regulate synaptic function, and their release can lead to paracrine actions on astrocytes as well as the regulation of neurotransmission.  The definition of a gliotransmitters is not only defined by its presence in glial cells, but is determined by other factors, including its metabolic pathway.  Also, the function of gliotransmitters varies according to their type, and each gliotransmitter has a specific target receptor and action.
Glial cells are important in hormonal and neuroendocrine function in the central nervous system and have an active role in sleep, cognition, synaptic function and plasticity, and promote remyelination and regeneration of injured nervous tissue.  Other functions include the regulation of neurosecretory neurons and the release of hormones.
ATP is a gliotransmitters that is released from astrocytes and restrains neuronal activity. ATP targets P2X receptors, P2Y, and A1 receptors.  ATP has several functions as a gliotransmitter, including injection of AMPA receptors into the postsynaptic terminal, paracrine activity through calcium waves in astrocytes, and suppression of synaptic transmission.  Neuronal activity is controlled in the retina by the molecule’s ability to hyperpolarize the neuron by converting from ATP to adenosine.  ATP plays a role in facilitating neuroinflammation and remyelination by entering into the cell’s extracellular space upon injury to activate purinergic receptors, which increase the production of gliotransmitters.  The mechanism of ATP release from astrocytes is not well understood. Although it is unclear whether or not ATP-mediated gliotransmission is calcium-dependent, it is believed that ATP release is partly dependent on Ca2+ and SNARE proteins and involves multiple pathways, with exocytosis being the suggested method of release. [4,11]
Other less common gliotransmitters include:
Gliotransmission can also occur between two types of glial cells: astrocytes and microglia.  Calcium waves within the intracellular matrix of the astrocyte can cause a response in microglia with the presence of ATP in the extracellular matrix. One study demonstrated that a mechanical stimulation caused astrocytes to release ATP, which in turn caused a delayed calcium response in microglia, suggesting that astrocyte-to-microglia communication could be mediated by ATP.
Communication between astrocytes and neurons is very important in neuronal function.  The “tripartite synapse” is that most common example of intercellular communication between astrocytes and neurons, and involves the pre- and postsynaptic terminals of two neurons and one astrocyte. Astrocytes have the ability to modulate neuronal activity, either causing exciting or inhibiting synaptic transmission, depending on the type of gliotransmitter released, specifically glutamate, which typically has excitatory influence on neurons, or ATP, which has shown to typically inhibit certain presynaptic functions of neurons. 
The astrocyte is bidirectional, meaning that is can communicate and exchange information with both pre- and postsynaptic elements. Communication is primarily controlled by the change in Ca2+ concentrations, causing excitability within the astrocyte.  The capability of a human to respond to change in both the external and internal environment is increased due to the hormonal regulation of the tripartite synapse. 
It is believed that certain neurodegenerative disorders, particularly schizophrenia and epilepsy, may be partially caused by varying levels of gliotransmission and calcium excitability.  One theory, called the glutamate hypothesis of schizophrenia, suggests that glutamate deficiency, which leads to the dysfunction of NMDARs at the presynaptic terminal, is believed to cause symptoms of schizophrenia. According to research, this hypofunctionality of NMDARs has been shown to be caused by lower amounts of gliotransmission facilitated by D-serine. The fact that cycloserine, which acts as an agonist for the NMDAR’s binding site, is used in the treatment for patients with schizophrenia further supports the glutamate hypothesis. In the case of epilepsy, it is known that glutamate plays a role in synchronous depolarizations.  This has led researchers to believe that excitation of epileptic discharges may be caused by the glutamate-mediated gliotransmission. Although that some studies show that the all excitations caused by gliotransmission lead to epileptic discharges, but it could possibly increase the intensity of length of epileptiform activity. 
The 5 first mentioned transmitters are primarily excitatory and can thus lead to neural apoptosis through excitotoxicity when expressed at large amounts. From neurodegenerative diseases, there is evidence at least for Alzheimer's disease that point to increased glial activation and amount (both glia and astrocyte) which accompanies simultaneous decrease in the amount of neurons. 
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