Article

The tripartite synapse: Roles for gliotransmission in health and disease

Silvio Conte Center for Integration at the Tripartite Synapse, Department of Neuroscience, University of Pennsylvania, School of Medicine Philadelphia, PA 19104, USA.
Trends in Molecular Medicine (Impact Factor: 10.11). 03/2007; 13(2):54-63. DOI: 10.1016/j.molmed.2006.12.005
Source: PubMed

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.

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    • "+ signals was positively correlated to spike frequency , and the duration of Ca 2+ signals was correlated with spike number . So , Ca 2+ levels in a neuron indicated its response strength in vivo ( Petersen et al . , 2005 ; Yaksi and Friedrich , 2006 ; Moreaux and Laurent , 2007 ) . The activity of the astrocytes also altered their Ca 2+ signals ( Halassa et al . , 2007 ) . The synchrony of Ca 2+ signals among cell pairs was analyzed by correlation coefficients to represent their activity synchrony ( Hirase et al . , 2004 ; Takata and Hirase , 2008 ; Golshani et al . , 2009 ) ."
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    • "While astrocytes are not electrically excitable like neurons, one mode of prominent activity of astrocytes is the release of calcium from internal stores following activation of a variety of G-protein coupled receptors. Many groups have hypothesized that calcium signaling in astrocytes underlies the release of many signaling molecules, termed 'gliotransmitters', which can directly impact neural circuit excitability [20]. While dynamic calcium transients have been readily observed in the somas and proximal thick processes of astrocytes maintained in culture and/or in brain slices prepared from very young animals, synthetic calcium-indicating dyes have been difficult to deliver in either adult or sclerotic tissue. "
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    • "This pathological astrocyte-neuron communication could be the key mechanism that determines seizure recurrence and epilepsy chronicity through the maintenance of an elevated glutamatergic tone. This work provides direct evidence of the pathophysiological role of astrocytes, demonstrating that altered astroglial signaling has severe effects on synaptic transmission, and supporting the idea that astroglial hyper or hypoactivation could take part in a broad spectrum of neurological disorders, as previously suggested (Devinsky et al., 2013; Halassa et al., 2007; Seifert et al., 2006). These findings support the pivotal role of astroglial Ca 21 signal and gliotransmission in pathophysiological conditions , providing a new perspective to advance toward understanding the biology of epilepsy and other brain diseases. "
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