Glutamate Released from Astrocytes Modulates Both Excitatory and Inhibitory Synaptic Transmission

al evidence suppor exocytotic pathway cytes (6, 44, 45). Astrocytic glutam ronal systems. At th been shown to ac important functional roles in the modulation of neuronal excitation was provided by the observations that these glial cells express neurotransmitter receptors. Because astrocytes express membrane receptors for almost all neurotransmitters (19), which are linked to IP3 production and release of Ca 2+ from intracellular stores, the astrocytic process can sense neurotransmitter released at the synapse leading to astrocyte activation through the mobilization of their intracellular Ca2+ (see FIGURE 2A). Activated astrocytes have the ability to release a variety of neuroactive molecules including glutamate, ATP, nitric oxide, prostaglandins, atrial natriuretic peptide (ANP), and D-serine, which in turn in uences neuronal excitability (4, 12, 30, 42). is bi-directional signaling between astrocytes and neurons has led us to propose that the astrocyte represents a third active element of the synapse together with the preand postsynaptic terminals in what we have termed the “tripartite synapse” (2). In the remainder of the discussion of the tripartite synapse, we will highlight some of the roles of two of these gliotransmitters, glutamate and ATP. By integrating experimental evidence provided by many laboratories, we will propose that the astrocyte serves a unique function in the nervous system and that by releasing two distinct transmitters the astrocyte provides spatially and temporally balanced excitation and inhibition to coordinate neuronal and synaptic networks.