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Astrocytes, a sub-type of glia in the central nervous system, are dynamic signaling elements that integrate neuronal inputs, exhibit calcium excitability, and can modulate neighboring neurons. Neuronal activity can lead to neurotransmitter-evoked activation of astrocytic receptors, which mobilizes their internal calcium. Elevations in astrocytic calcium in turn trigger the release of chemical transmitters from astrocytes, which can cause sustained modulatory actions on neighboring neurons. Astrocytes, and perisynaptic Schwann cells, by virtue of their intimate association with synapses, are strategically positioned to regulate synaptic transmission. This capability, that has now been demonstrated in several studies, raises the untested possibility that astrocytes are an integral element of the circuitry for synaptic plasticity. Because the highest ratio of glia-to-neurons is found at the top of the phylogenetic tree in the human brain, these recent demonstrations of dynamic bi-directional signaling between astrocytes and neurons leave us with the question as to whether astrocytes are key regulatory elements of higher cortical functions.
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Structure of Astrocytes: Astrocytes are numerous and are intimately associated with neurons. A set of images is provided which demonstrates some of the structural features of these astrocytes. Astrocytes and their peripheral homologs, perisynaptic Schwann cells, make intimate contact with synapses. Glutamine synthetase labelled astrocytes in stratum radiatum of rat hippocampus (Amin Derouiche): Glutamine synthetase labelled astrocytes in stratum radiatum of rat hippocampus (Amin Derouiche): Double stain of lizard nerve terminal (red) and perisynaptic Schwann cells (green) (Clark Lindgren): Calcium Signals in Astrocytes: Instead of utilizing fluctuations in membrane potential as a signaling mechanism, oscillations of intracellular calcium represent the form of excitability of astrocytes. In this section several examples of calcium signals in astrocytes are provided. Significant evidence now supports the concept of an extracellular signal (ATP) being necessary for calcium waves. In support of this notion, perfusion of the external saline directs the propagation of a calcium wave, and calcium waves can propagate beyond cell free boundaries as a result of a ATP diffusion. Calcium wave amongst cell cultured astrocytes (Barbara Innocenti and Philip Haydon) (click image to download MPG file): Calcium wave crossing a cell free lane providing evidence for an extracellular signal (Stanley Kater) (click image to download MPG file): Movie of glutamate wave over cultured astrocytes (Barbara Innocenti and Philip Haydon) (click image to download MPG file): Summary: Astrocytes are intimately associated with the pre and postsynaptic terminals of chemical synapses, and, since they can both receive signals from and send modulatory signals to these nerve terminals, they can be considered as intimate partners in tripartite synapses. The animated image beneath summarizes a current working hypothesis about the relationship between astrocytes and synaptic terminals. In this diagram, the general term glia is utilized since the concepts shown are shared by the neuromuscular junction and associated perisynaptic Schwann cells.