| OCR Text |
Show 5 intracellular calcium rise motivated a shift in how neuroscientists think about the brain (Cornell-Bell et al., 1990). Since this discovery, it has become well established that astrocytes sense synaptic activity through many different types of receptors specific for neurotransmitters including glutamate, adenosine trisphosphate (ATP) and gammaaminobutyric acid (GABA; Ahmed et al., 1990; Cornell-Bell et al., 1990; Fraser et al., 1994, 1995; Kim et al., 1994; Neary et al., 1991; Porter and McCarthy, 1995). The subsequent discovery that astrocytes can, in some circumstances, release signaling molecules termed "gliotransmitters" in a calcium-dependent fashion led to the concept of the "tripartite synapse" (Araque et al., 1999). The tripartite synapse hypothesis proposes that the synapse consists of three functional units including the pre- and postsynaptic neuronal components and an astrocyte process which can modulate synaptic activity through release of gliotransmitters such as glutamate, ATP and D-serine (Araque et al., 1999). This model predicts that astrocytes play an active role in neuronal network dynamics via modulation of synaptic activity. However, this hypothesis has been challenged and may actually be a phenomenon that only exists in astrocyte culture or pathological conditions (Hamilton and Attwell, 2010; Petravicz et al., 2008). Other roles for astrocytic process calcium activity have been proposed, as well. A recent study demonstrated that glutamate-induced astrocytic calcium rises in distal processes encourage actin-mediated and activity-dependent process extension around the neuronal synapse (Bernardinelli et al., 2014). In this way, astrocytic processes can prevent spillover of neurotransmitter to adjacent synapses and increase synaptic contact area for more efficient uptake of neurotransmitter via membrane transporters. Calcium signaling can regulate gene transcription and modification of protein structure and activity (Gottfried et al., 1999; Kubes et al., 1998; Rodnight et al., 1997). |
