The tripartite synapse: roles for gliotransmission in health and disease.
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.
Halassa
Michael M
MM
Silvio Conte Center for Integration at the Tripartite Synapse, Department of Neuroscience, University of Pennsylvania, School of Medicine Philadelphia, PA 19104, USA.
Fellin
Tommaso
T
Haydon
Philip G
PG
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000502:physiology / Q000648:ultrastructure; D020013:Calcium Signaling; D004827:Epilepsy / Q000209:etiology / Q000503:physiopathology; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D008959:Models, Neurological; D009473:Neuronal Plasticity; D018377:Neurotransmitter Agents / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012559:Schizophrenia / Q000209:etiology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000503:physiopathology; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*
D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D000255:Adenosine Triphosphate