Abstract
Background: Activation of G protein coupled receptor (GPCR) in astrocytes leads to Ca2+-dependent glutamate release via Bestrophin 1 (Best1) channel. Whether receptor-mediated glutamate release from astrocytes can regulate synaptic plasticity remains to be fully understood. Results: We show here that Best1-mediated astrocytic glutamate activates the synaptic N-methyl-D-aspartate receptor (NMDAR) and modulates NMDAR-dependent synaptic plasticity. Our data show that activation of the protease-activated receptor 1 (PAR1) in hippocampal CA1 astrocytes elevates the glutamate concentration at Schaffer collateral-CA1 (SC-CA1) synapses, resulting in activation of GluN2A-containing NMDARs and NMDAR-dependent potentiation of synaptic responses. Furthermore, the threshold for inducing NMDAR-dependent long-term potentiation (LTP) is lowered when astrocytic glutamate release accompanied LTP induction, suggesting that astrocytic glutamate is significant in modulating synaptic plasticity. Conclusions: Our results provide direct evidence for the physiological importance of channel-mediated astrocytic glutamate in modulating neural circuit functions.
| Original language | English |
|---|---|
| Article number | 7 |
| Journal | Molecular Brain |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2015 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience
- Molecular Biology
- Medicine(all)
Cite this
Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors. / Park, Hyungju; Han, Kyung Seok; Seo, Jinsoo; Lee, Jaekwang; Dravid, Shashank M.; Woo, Junsung; Chun, Heejung; Cho, Sukhee; Bae, Jin Young; An, Heeyoung; Koh, Woohyun; Yoon, Bo Eun; Berlinguer-Palmini, Rolando; Mannaioni, Guido; Traynelis, Stephen F.; Bae, Yong Chul; Choi, Se Young; Lee, C. Justin.
In: Molecular Brain, Vol. 8, No. 1, 7, 2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors
AU - Park, Hyungju
AU - Han, Kyung Seok
AU - Seo, Jinsoo
AU - Lee, Jaekwang
AU - Dravid, Shashank M.
AU - Woo, Junsung
AU - Chun, Heejung
AU - Cho, Sukhee
AU - Bae, Jin Young
AU - An, Heeyoung
AU - Koh, Woohyun
AU - Yoon, Bo Eun
AU - Berlinguer-Palmini, Rolando
AU - Mannaioni, Guido
AU - Traynelis, Stephen F.
AU - Bae, Yong Chul
AU - Choi, Se Young
AU - Lee, C. Justin
PY - 2015
Y1 - 2015
N2 - Background: Activation of G protein coupled receptor (GPCR) in astrocytes leads to Ca2+-dependent glutamate release via Bestrophin 1 (Best1) channel. Whether receptor-mediated glutamate release from astrocytes can regulate synaptic plasticity remains to be fully understood. Results: We show here that Best1-mediated astrocytic glutamate activates the synaptic N-methyl-D-aspartate receptor (NMDAR) and modulates NMDAR-dependent synaptic plasticity. Our data show that activation of the protease-activated receptor 1 (PAR1) in hippocampal CA1 astrocytes elevates the glutamate concentration at Schaffer collateral-CA1 (SC-CA1) synapses, resulting in activation of GluN2A-containing NMDARs and NMDAR-dependent potentiation of synaptic responses. Furthermore, the threshold for inducing NMDAR-dependent long-term potentiation (LTP) is lowered when astrocytic glutamate release accompanied LTP induction, suggesting that astrocytic glutamate is significant in modulating synaptic plasticity. Conclusions: Our results provide direct evidence for the physiological importance of channel-mediated astrocytic glutamate in modulating neural circuit functions.
AB - Background: Activation of G protein coupled receptor (GPCR) in astrocytes leads to Ca2+-dependent glutamate release via Bestrophin 1 (Best1) channel. Whether receptor-mediated glutamate release from astrocytes can regulate synaptic plasticity remains to be fully understood. Results: We show here that Best1-mediated astrocytic glutamate activates the synaptic N-methyl-D-aspartate receptor (NMDAR) and modulates NMDAR-dependent synaptic plasticity. Our data show that activation of the protease-activated receptor 1 (PAR1) in hippocampal CA1 astrocytes elevates the glutamate concentration at Schaffer collateral-CA1 (SC-CA1) synapses, resulting in activation of GluN2A-containing NMDARs and NMDAR-dependent potentiation of synaptic responses. Furthermore, the threshold for inducing NMDAR-dependent long-term potentiation (LTP) is lowered when astrocytic glutamate release accompanied LTP induction, suggesting that astrocytic glutamate is significant in modulating synaptic plasticity. Conclusions: Our results provide direct evidence for the physiological importance of channel-mediated astrocytic glutamate in modulating neural circuit functions.
UR - http://www.scopus.com/inward/record.url?scp=84924190787&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924190787&partnerID=8YFLogxK
U2 - 10.1186/s13041-015-0097-y
DO - 10.1186/s13041-015-0097-y
M3 - Article
VL - 8
JO - Molecular Brain
JF - Molecular Brain
SN - 1756-6606
IS - 1
M1 - 7
ER -