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Brain Struct Funct. 2019 Nov;224(8):2691-2701. doi: 10.1007/s00429-019-01925-6. Epub 2019 Aug 2.

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

Author information

1
Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland.
2
Laboratory of Molecular Basis of Behavior, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland.
3
Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland. k.kalita@nencki.gov.pl.

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.

KEYWORDS:

Cofilin 1; Dentate gyrus; Rodent-specific behaviors; Serum response factor; Structural plasticity

PMID:
31375980
DOI:
10.1007/s00429-019-01925-6
Free PMC Article

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