Journal Article

DZNE-2021-00115

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Serotonin receptor 4 regulates hippocampal astrocyte morphology and function.

Müller, F. E. ; Schade, S. K. ; Cherkas, V. ; Stopper, L. ; Breithausen, B. ; Minge, D. ; Varbanov, H. ; Wahl-Schott, C. ; Antoniuk, S. ; Domingos, C. ; Compan, V. ; Kirchhoff, F. ; Henneberger, C.DZNE* ; Ponimaskin, E. (Corresponding author) ; Zeug, A. (Corresponding author)

2021
Wiley-Liss Bognor Regis [u.a.]

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Please use a persistent id in citations: doi:10.1002/glia.23933

Abstract: 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.

Keyword(s): Astrocytes (MeSH) ; Excitatory Postsynaptic Potentials (MeSH) ; Hippocampus (MeSH) ; Receptors, Serotonin: genetics (MeSH) ; Serotonin (MeSH) ; Synaptic Transmission (MeSH) ; 5-ht Zeug ; RhoA ; actin ; astrocytes ; neuronal excitability ; serotonin

Note: ISSN 1098-1136 not unique: **3 hits**.

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Contributing Institute(s):

1. U Preclinical Researchers - Bonn (U Preclinical Researchers - Bonn)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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