Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses

Mika Tanaka,Shigeyoshi Itohara,Junichi Nakai,Pei-Yu Shih,Alexey Semyanov,Teiichi Furuichi,Hiroshi Gomi,Katsuhiko Mikoshiba,Takamasa Yoshida,Reiko Ando

doi:10.1186/1756-6606-6-6

Abstract

BackgroundNeuronal activity alters calcium ion (Ca2+) dynamics in astrocytes, but the physiologic relevance of these changes is controversial. To examine this issue further, we generated an inducible transgenic mouse model in which the expression of an inositol 1,4,5-trisphosphate absorbent, “IP3 sponge”, attenuates astrocytic Ca2+ signaling.ResultsAttenuated Ca2+ activity correlated with reduced astrocytic coverage of asymmetric synapses in the hippocampal CA1 region in these animals. The decreased astrocytic ‘protection’ of the synapses facilitated glutamate ‘spillover’, which was reflected by prolonged glutamate transporter currents in stratum radiatum astrocytes and enhanced N-methyl-D-aspartate receptor currents in CA1 pyramidal neurons in response to burst stimulation. These mice also exhibited behavioral impairments in spatial reference memory and remote contextual fear memory, in which hippocampal circuits are involved.ConclusionsOur findings suggest that IP3-mediated astrocytic Ca2+ signaling correlates with the formation of functional tripartite synapses in the hippocampus.

Highlights

Neuronal activity alters calcium ion (Ca2+) dynamics in astrocytes, but the physiologic relevance of these changes is controversial
Attenuated agonist-evoked IICR in astrocytes by IP3 buffering with a glutathione-S-transferase (GST)-IP3 sponge To investigate the in vivo role of Ca2+ dynamics in astrocytes, we generated two transgenic mouse lines (Figure 1A) in which IICR was attenuated by the expression of an IP3 absorbent “IP3 sponge” [13] in an astrocyte-specific and temporally controlled manner
In the Tg1:tetO-G-CaMP2 and GLT-1tTA (Tg2) double transgenic (DTg) mice, lacZ reporter expression was efficiently induced in broad brain areas except for the cerebellum (Figure 1, B and C)

Summary

Introduction

Neuronal activity alters calcium ion (Ca2+) dynamics in astrocytes, but the physiologic relevance of these changes is controversial To examine this issue further, we generated an inducible transgenic mouse model in which the expression of an inositol 1,4,5-trisphosphate absorbent, “IP3 sponge”, attenuates astrocytic Ca2+ signaling. The decreased astrocytic ‘protection’ of the synapses facilitated glutamate ‘spillover’, which was reflected by prolonged glutamate transporter currents in stratum radiatum astrocytes and enhanced N-methyl-D-aspartate receptor currents in CA1 pyramidal neurons in response to burst stimulation. These mice exhibited behavioral impairments in spatial reference memory and remote contextual fear memory, in which hippocampal circuits are involved. We generated a new mouse model in which

Methods

Results

Conclusion