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Serotonin receptor 4 regulates hippocampal astrocyte morphology and function
Author(s) -
Müller Franziska E.,
Schade Sophie K.,
Cherkas Volodymyr,
Stopper Laura,
Breithausen Björn,
Minge Daniel,
Varbanov Hristo,
WahlSchott Christian,
Antoniuk Svitlana,
Domingos Catia,
Compan Valérie,
Kirchhoff Frank,
Henneberger Christian,
Ponimaskin Evgeni,
Zeug Andre
Publication year - 2021
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23933
Subject(s) - excitatory postsynaptic potential , biology , rhoa , neuroscience , glutamatergic , astrocyte , hippocampal formation , postsynaptic potential , neurotransmission , microbiology and biotechnology , inhibitory postsynaptic potential , signal transduction , receptor , glutamate receptor , central nervous system , biochemistry
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‐HT 4 R) is expressed in hippocampal astrocytes, both in vitro and in vivo. Through fluorescence microscopy, we established that 5‐HT 4 R activation triggered RhoA activity via Gα 13 ‐mediated signaling, which boosted filamentous actin assembly, leading to morphological changes in hippocampal astrocytes. We investigated the effects of these 5‐HT 4 R‐mediated changes in mixed cultures and in acute slices, in which 5‐HT 4 R was expressed exclusively in astrocytes. In both systems, 5‐HT 4 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‐HT 4 R‐Gα 13 ‐RhoA signaling is a previously unrecognized molecular pathway involved in the functional regulation of excitatory synaptic circuits.