Accumulating evidence indicates that astrocytes are actively involved in brain function by regulating synaptic activity and plasticity. Different gliotransmitters, such as glutamate, ATP, GABA or D-serine, released form astrocytes have been shown to induce different forms of synaptic regulation. However, whether a single astrocyte may release different gliotransmitters is unknown. Here we show that mouse hippocampal astrocytes activated by endogenous (neuron-released endocannabinoids or GABA) or exogenous (single astrocyte Ca2+ uncaging) stimuli modulate putative single CA3-CA1 hippocampal synapses. The astrocyte-mediated synaptic modulation was biphasic and consisted of an initial glutamate-mediated potentiation followed by a purinergicmediated depression of neurotransmitter release. The temporal dynamic properties of this biphasic synaptic regulation depended on the firing frequency and duration of the neuronal activity that stimulated astrocytes. Present results indicate that single astrocytes can decode neuronal activity and, in response, release distinct gliotransmitters to differentially regulate neurotransmission at putative single synapses.
Bibliographical noteFunding Information:
We thank R Quintana and S Jamison for technical help; Dr. J Chen (UCSD, USA) for providing IP3R2-null mice; Dr. G Marsicano for providing the GFAP-CB1-null; Dr. F Kirchhoff, Dr. D E Bergles and Dr. A Agarwal for providing the astroglial GABAB-null and GCaMP3 mice; and Dr. R Gomez, Dr. A Diez, M Martin-Fernandez, C Durkee, J Lines, M Corkrum and A Ferro for helpful suggestions. This work was supported by NIH-NINDS (R01NS097312-01) and Human Frontier Science Program (Research Grant RGP0036/2014) to AA. The authors declare no financial competing interests.
Human Frontier Science Program RGP0036/2014 Alfonso Araque. National Institute of Neurological Disorders and Stroke R01NS097312-01 Alfonso Araque.