Astroglia affect neuronal synaptic transmission in several ways. First, astrocytes modulate synaptic strength by controlling the concentration of neurotransmitter in the cleft via glial transporters. This is the case for most synapses that use amino acid neurotransmitters, such as glutamate, GABA, and monoamines, where astrocytes express specific transporters, depending on the synapse (see Chapter 5.7). Alternative mechanisms of affecting neurotransmitter concentration exist in central cholinergic synapses; astrocytes covering these synapses are able to synthesize and release the acetylcholine binding protein (AChBP), which structurally is similar to the nicotinic cholinoreceptor and has a high-affinity binding site for ACh. Extensive stimulation of cholinergic terminals enhances the release of AChBP, which enters the synaptic cleft, binds ACh and effectively lowers the concentration of the latter, thus attenuating the synaptic strength.
Second, 'glio' transmitters released from astrocytes also affect synaptic transmission in neighbouring neuronal circuits. In fact, astrocytes are capable of exerting multiple effects on this ongoing neurotransmission. For example, in hippocampal neurones cultured together with astrocytes, the stimulation of the latter increased the frequency of spontaneous (miniature) excitatory and inhibitory postsynaptic currents, but decreased the amplitude of the evoked postsynaptic responses (Figure 7.13). This difference was explained through activation of two independent pathways: in the former case, glutamate acted via presynaptic NMDA receptors (which are active already at low glutamate concentrations), whereas the latter effect was mediated through presynaptic metabotropic glutamate receptors. Astroglial glutamate release may also affect inhibitory pathways in the hippocampus, by facilitating GABA release from interneurones connected to pyramidal CA1 cells; this effect is mediated by activation of ionotropic glutamate receptors of the kainate subtype, located in the terminals of the interneurones.
Astrocytes are also capable of modulating synaptic transmission through the release of ATP. In hippocampal neuronal-glial co-cultures, ATP secreted by astrocytes inhibited glutamatergic synapses via presynaptic metabotropic (P2Y) puri-noreceptors. Alternatively, as was shown in experiments in hippocampal slices, ATP released by astrocytes was catalyzed by ectoenzymes into adenosine, which produced tonic suppression of synaptic transmission by acting on adenosine receptors. Similar effects have been observed in the retina, where ATP released from Müller cells degrades to adenosine and inhibits neurones acting through adenosine receptors.
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