| OCR Text |
Show 91 structures. Although many calcium-dependent pathways have been described in detail, the downstream effects of cytosolic calcium are not well understood or well characterized. Calcium plays a major role the astrocytic response to environmental signals. These signals are involved in sensing neurotransmitters, temperature and osmotic changes (Cornell-Bell et al., 1990; Schipke et al., 2008). Calcium may regulate the amount of astrocyte process synaptic coverage in an activity-dependent fashion (Bernardinelli et al., 2014). By sensing glutamate release from excitatory synapses, astrocytes can extend or retract the process through actin polymerization. In this way, astrocytes can modify the synaptic contact surface area in order to prevent neurotransmitter spillover into adjacent synapses or change the amount of neurotransmitter uptake via membrane transporters (Bernardinelli et al., 2014). The tripartite synapse model predicts that astrocytes respond to neurotransmitter receptor binding with an intracellular calcium transient which, in turn, induces a calciumdependent exocytosis of gliotransmitters, such as glutamate, ATP or D-serine (Araque et al., 1999). The model proposes that, in this way, astrocytes play a role in modulating synaptic neurotransmission and neuronal network activity. Astrocytic terminal process calcium transients have been implicated in long-term potentiation (LTP) of excitatory synapses in the mammalian hippocampus (Henneberger et al., 2010). However, this prediction has been challenged by LTP experiments in which the IP3R2-KO mouse line, which does not express IP3 receptor 2 and thus compromises IP3-dependent intracellular calcium signaling in astrocytes, failed to display a difference in LTP relative to controls (Petravicz et al., 2008). More recent work has demonstrated that terminal process calcium activity remains intact in the IP3R2-KO mouse line, so it is likely that terminal process stores are not IP3-dependent and may actually depend on extracellular stores (Srinivasan |
