The tripartite synapse: roles for gliotransmission in health and disease.
ABSTRACT In addition to being essential supporters of neuronal function, astrocytes are now recognized as active elements in the brain. Astrocytes sense and integrate synaptic activity and, depending on intracellular Ca(2+) levels, release gliotransmitters (e.g. glutamate, d-serine and ATP) that have feedback actions on neurons. Recent experimental results have raised the possibility that quantitative variations in gliotransmission might contribute to disorders of the nervous system. Here, we discuss targeted molecular genetic approaches that have demonstrated that alterations in protein expression in astrocytes can lead to serious changes in neuronal function. We also introduce the concept of 'astrocyte activation spectrum' in which enhanced and reduced gliotransmission might contribute to epilepsy and schizophrenia, respectively. The results of future experimental tests of the astrocyte activation spectrum, which relates gliotransmission to neurological and psychiatric disorders, might point to a new therapeutic target in the brain.
SourceAvailable from: Janosch Peter Heller[Show abstract] [Hide abstract]
ABSTRACT: Memory formation in the brain is thought to rely on the remodeling of synaptic connections which eventually results in neural network rewiring. This remodeling is likely to involve ultrathin astroglial protrusions which often occur in the immediate vicinity of excitatory synapses. The phenomenology, cellular mechanisms, and causal relationships of such astroglial restructuring remain, however, poorly understood. This is in large part because monitoring and probing of the underpinning molecular machinery on the scale of nanoscopic astroglial compartments remains a challenge. Here we briefly summarize the current knowledge regarding the cellular organisation of astroglia in the synaptic microenvironment and discuss molecular mechanisms potentially involved in use-dependent astroglial morphogenesis. We also discuss recent observations concerning morphological astroglial plasticity, the respective monitoring methods, and some of the newly emerging techniques that might help with conceptual advances in the area. GLIA 2015. © 2015 The Authors. Glia Published by Wiley Periodicals, Inc.Glia 03/2015; DOI:10.1002/glia.22821 · 5.47 Impact Factor
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ABSTRACT: It is increasingly evident that astrocytes, once considered primarily a passive support cell type, in fact respond to and regulate neurotransmission to influence information processing and behavior. Although astrocytes are not electrically excitable, they express a variety of receptors that produce calcium responses able to propagate within and between astrocytes. This form of signaling occurs on spatial and temporal scales distinct from those of neuronal activity, potentially allowing astrocytes to locally regulate synaptic and network activity over extended time periods. Perhaps the best studied example of this regulation is the control of sleep homeostasis by astrocytes. Astrocyte-derived adenosine causes an increase in sleep pressure leading to increased slow wave activity and extended recovery sleep. Despite its established importance for the sleep homeostat, however, the roles of astrocytes in other sleep-associated processes are only beginning to be understood.03/2015; 1(1):9-19. DOI:10.1007/s40675-014-0005-5
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ABSTRACT: Astrocytes and neurons are inseparable partners in the brain. Neurotransmitters released from neurons activate corresponding G protein-coupled receptors (GPCR) expressed in astrocytes, resulting in release of gliotransmitters such as glutamate, D-serine, and ATP. These gliotransmitters in turn influence neuronal excitability and synaptic activities. Among these gliotransmitters, ATP regulates the level of network excitability and is critically involved in sleep homeostasis and astrocytic Ca(2+) oscillations. ATP is known to be released from astrocytes by Ca(2+)-dependent manner. However, the precise source of Ca(2+), whether it is Ca(2+) entry from outside of cell or from the intracellular store, is still not clear yet. Here, we performed sniffer patch to detect ATP release from astrocyte by using various stimulation. We found that ATP was not released from astrocyte when Ca(2+) was released from intracellular stores by activation of Gαq-coupled GPCR including PAR1, P2YR, and B2R. More importantly, mechanical stimulation (MS)-induced ATP release from astrocyte was eliminated when external Ca(2+) was omitted. Our results suggest that Ca(2+) entry, but not release from intracellular Ca(2+) store, is critical for MS-induced ATP release from astrocyte.03/2015; 24(1):17-23. DOI:10.5607/en.2015.24.1.17