title: Glutamate mediated astrocytic filtering of neuronal activity.
abstract: Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity.
authors.affiliation: School of Electrical Engineering, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: Gilad
authors.initials: G
authors.lastname: Wallach
authors.affiliation: Team Beagle, INRIA Rhone-Alpes, Villeurbanne, France; University of Lyon, LIRIS UMR5205, Villeurbanne, France.
authors.forename: Jules
authors.initials: J
authors.lastname: Lallouette
authors.affiliation: School of Electrical Engineering, Tel Aviv University, Ramat Aviv, Israel; Department of Electrical and Electronic Engineering, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Nitzan
authors.initials: N
authors.lastname: Herzog
authors.affiliation: School of Electrical Engineering, Tel Aviv University, Ramat Aviv, Israel; Team Beagle, INRIA Rhone-Alpes, Villeurbanne, France; University of Lyon, LIRIS UMR5205, Villeurbanne, France; School of Physics and Astronomy, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: Maurizio
authors.initials: M
authors.lastname: De Pittà
authors.affiliation: School of Physics and Astronomy, Tel Aviv University, Ramat Aviv, Israel; Center for Theoretical Biological Physics, Rice University, Houston, Texas, United States of America.
authors.forename: Eshel
authors.initials: E
authors.lastname: Ben Jacob
authors.affiliation: Team Beagle, INRIA Rhone-Alpes, Villeurbanne, France; University of Lyon, LIRIS UMR5205, Villeurbanne, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Berry
authors.affiliation: School of Electrical Engineering, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Hanein
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D019295:Computational Biology; D018698:Glutamic Acid / Q000378:metabolism*; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism / Q000502:physiology
chemical_list: D018698:Glutamic Acid; D002118:Calcium