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


RESULTS
Attenuated 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.


CONCLUSIONS
Our findings suggest that IP3-mediated astrocytic Ca2+ signaling correlates with the formation of functional tripartite synapses in the hippocampus.
RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, 351-0198, Japan.
Mika
M
Tanaka
Pei-Yu
PY
Shih
Hiroshi
H
Gomi
Takamasa
T
Yoshida
Junichi
J
Nakai
Reiko
R
Ando
Teiichi
T
Furuichi
Katsuhiko
K
Mikoshiba
Alexey
A
Semyanov
Shigeyoshi
S
Itohara
D000818:Animals; D001007:Anxiety / Q000473:pathology / Q000503:physiopathology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008568:Memory / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
D005971:Glutamates; D015544:Inositol 1,4,5-Trisphosphate; D005982:Glutathione Transferase; D002118:Calcium