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: 9.45). 03/2007; 13(2):54-63. DOI: 10.1016/j.molmed.2006.12.005
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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- "O ver the last decade the glial cell astrocytes, beyond their broad control of brain tissue homeostasis and metabolism , have been recognized to regulate neuronal network activities (Araque et al., 2001; Carmignoto, 2000; Halassa et al., 2007; Haydon and Carmignoto, 2006; Perea et al., 2009; Volterra and Meldolesi, 2005). Indeed, astrocytes can modulate synaptic transmission and contribute to important phenomena in brain function thanks to a dynamic interaction with neurons that is finely regulated in time and space (Araque et al., 2014). "
ABSTRACT: Studies over the last decade provided evidence that in a dynamic interaction with neurons glial cell astrocytes contribut to fundamental phenomena in the brain. Most of the knowledge on this derives, however, from studies monitoring the astrocyte Ca(2+) response to glutamate. Whether astrocytes can similarly respond to other neurotransmitters, including the inhibitory neurotransmitter GABA, is relatively unexplored. By using confocal and two photon laser-scanning microscopy the astrocyte response to GABA in the mouse somatosensory and temporal cortex was studied. In slices from developing (P15-20) and adult (P30-60) mice, it was found that in a subpopulation of astrocytes GABA evoked somatic Ca(2+) oscillations. This response was mediated by GABAB receptors and involved both Gi/o protein and inositol 1,4,5-trisphosphate (IP3 ) signalling pathways. In vivo experiments from young adult mice, revealed that also cortical astrocytes in the living brain exibit GABAB receptor-mediated Ca(2+) elevations. At all astrocytic processes tested, local GABA or Baclofen brief applications induced long-lasting Ca(2+) oscillations, suggesting that all astrocytes have the potential to respond to GABA. Finally, in patch-clamp recordings it was found that Ca(2+) oscillations induced by Baclofen evoked astrocytic glutamate release and slow inward currents (SICs) in pyramidal cells from wild type but not IP3 R2(-/-) mice, in which astrocytic GABAB receptor-mediated Ca(2+) elevations are impaired. These data suggest that cortical astrocytes in the mouse brain can sense the activity of GABAergic interneurons and through their specific recruitment contribut to the distinct role played on the cortical network by the different subsets of GABAergic interneurons. GLIA 2015.Glia 10/2015; DOI:10.1002/glia.22933 · 6.03 Impact Factor
- "TNF-alpha is one of only a handful of recognized gliotransmitters. TNF-alpha released by glia, has been demonstrated to control synaptic strength. NSAIDS inhibit COX enzymes and thereby decrease the production of cytokines & microglial activation, platelet aggregation, iNOS and beta secretase. "
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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 ) ."
ABSTRACT: Associative learning and memory are essential to logical thinking and cognition. How the neurons are recruited as associative memory cells to encode multiple input signals for their associated storage and distinguishable retrieval remains unclear. We studied this issue in the barrel cortex by in vivo two-photon calcium imaging, electrophysiology, and neural tracing in our mouse model that the simultaneous whisker and olfaction stimulations led to odorant-induced whisker motion. After this cross-modal reflex arose, the barrel and piriform cortices connected. More than 40% of barrel cortical neurons became to encode odor signal alongside whisker signal. Some of these neurons expressed distinct activity patterns in response to acquired odor signal and innate whisker signal, and others encoded similar pattern in response to these signals. In the meantime, certain barrel cortical astrocytes encoded odorant and whisker signals. After associative learning, the neurons and astrocytes in the sensory cortices are able to store the newly learnt signal (cross-modal memory) besides the innate signal (native-modal memory). Such associative memory cells distinguish the differences of these signals by programming different codes and signify the historical associations of these signals by similar codes in information retrievals.Frontiers in Cellular Neuroscience 08/2015; 9(320):1-17. DOI:10.3389/fncel.2015.00320 · 4.29 Impact Factor
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