TY  - JOUR
AU  - Müller, Franziska E
AU  - Schade, Sophie K
AU  - Cherkas, Volodymyr
AU  - Stopper, Laura
AU  - Breithausen, Björn
AU  - Minge, Daniel
AU  - Varbanov, Hristo
AU  - Wahl-Schott, Christian
AU  - Antoniuk, Svitlana
AU  - Domingos, Catia
AU  - Compan, Valérie
AU  - Kirchhoff, Frank
AU  - Henneberger, Christian
AU  - Ponimaskin, Evgeni
AU  - Zeug, Andre
TI  - Serotonin receptor 4 regulates hippocampal astrocyte morphology and function.
JO  - Glia
VL  - 69
IS  - 4
SN  - 1098-1136
CY  - Bognor Regis [u.a.]
PB  - Wiley-Liss
M1  - DZNE-2021-00115
SP  - 872 - 889
PY  - 2021
N1  - ISSN 1098-1136 not unique: **3 hits**.
AB  - Astrocytes are an important component of the multipartite synapse and crucial for proper neuronal network function. Although small GTPases of the Rho family are powerful regulators of cellular morphology, the signaling modules of Rho-mediated pathways in astrocytes remain enigmatic. Here we demonstrated that the serotonin receptor 4 (5-HT4 R) is expressed in hippocampal astrocytes, both in vitro and in vivo. Through fluorescence microscopy, we established that 5-HT4 R activation triggered RhoA activity via Gα13 -mediated signaling, which boosted filamentous actin assembly, leading to morphological changes in hippocampal astrocytes. We investigated the effects of these 5-HT4 R-mediated changes in mixed cultures and in acute slices, in which 5-HT4 R was expressed exclusively in astrocytes. In both systems, 5-HT4 R-RhoA signaling changed glutamatergic synaptic transmission: It increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in mixed cultures and reduced the paired-pulse-ratio (PPR) of field excitatory postsynaptic potentials (fEPSPs) in acute slices. Overall, our present findings demonstrate that astrocytic 5-HT4 R-Gα13 -RhoA signaling is a previously unrecognized molecular pathway involved in the functional regulation of excitatory synaptic circuits.
KW  - Astrocytes
KW  - Excitatory Postsynaptic Potentials
KW  - Hippocampus
KW  - Receptors, Serotonin: genetics
KW  - Serotonin
KW  - Synaptic Transmission
KW  - 5-ht Zeug (Other)
KW  - RhoA (Other)
KW  - actin (Other)
KW  - astrocytes (Other)
KW  - neuronal excitability (Other)
KW  - serotonin (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33156956
DO  - DOI:10.1002/glia.23933
UR  - https://pub.dzne.de/record/154261
ER  -