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Open Access 01-11-2019 | Original Article

Loss of serum response factor in mature neurons in the dentate gyrus alters the morphology of dendritic spines and hippocampus-dependent behavioral tasks

Authors: Karolina Nader, Anna Krysiak, Anna Beroun, Martyna Pekala, Magda Szymanska, Bozena Kuzniewska, Kasia Radwanska, Leszek Kaczmarek, Katarzyna Kalita

Published in: Brain Structure and Function | Issue 8/2019

Abstract

Serum response factor (SRF) is a major transcription factor that regulates the expression of several plasticity-associated genes in the brain. Although the developmental expression of SRF in excitatory neurons is crucial for establishing proper hippocampal circuitry, no substantial evidence of its role in unstimulated mature neurons has been provided. The present study used time-controlled, conditional SRF knockout mice and found that the lack of SRF in adult neurons led to decreased actin levels and inactivation of the actin-severing protein cofilin 1 through its increase in phosphorylation at Ser3. The augmentation of cofilin 1 phosphorylation correlated with an alteration of dendritic spine morphology in the dentate gyrus, which was reflected by an increase in the number of spines that clustered into the long-spine category. The changes in spine morphology coincided with a lower amplitude and frequency of miniature excitatory postsynaptic currents. Moreover, SRF knockout animals were hyperactive and exhibited impairments in hippocampus-dependent behaviors, such as digging, marble burying, and nesting. Altogether, our data indicate that the adult deletion of neuronal SRF leads to alterations of spine morphology and function and hippocampus-dependent behaviors. Thus, SRF deletion in adult neurons recapitulates some aspects of morphological, electrophysiological, and behavioral changes that are observed in such psychiatric disorders as schizophrenia and autism spectrum disorders.

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Title: Loss of serum response factor in mature neurons in the dentate gyrus alters the morphology of dendritic spines and hippocampus-dependent behavioral tasks
Authors: Karolina Nader
Anna Krysiak
Anna Beroun
Martyna Pekala
Magda Szymanska
Bozena Kuzniewska
Kasia Radwanska
Leszek Kaczmarek
Katarzyna Kalita
Publication date: 01-11-2019
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 8/2019
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-019-01925-6

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Loss of serum response factor in mature neurons in the dentate gyrus alters the morphology of dendritic spines and hippocampus-dependent behavioral tasks

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