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Enriched Environment and Social Isolation Affect Cognition Ability via Altering Excitatory and Inhibitory Synaptic Density in Mice Hippocampus

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Abstract

The purpose of the study was to examine whether the underlying mechanism of the alteration of cognitive ability and synaptic plasticity induced by the housing environment is associated with the balance of excitatory/inhibitory synaptic density. Enriched environment (EE) and social isolation (SI) are two different housing environment, and one is to give multiple sensory environments, the other is to give monotonous and lonely environment. Male 4-week-old C57 mice were divided into three groups: CON, EE and SI. They were housed in the different cage until 3 months of age. Morris water maze and novel object recognition were performed. Long term potentiation (LTP), depotentiation (DEP) and local field potentials were recorded in the hippocampal perforant pathway and dentate gyrus (DG) region. The data showed that EE enhanced the ability of spatial learning, reversal learning and memory as well as LTP/DEP in the hippocampal DG region. Meanwhile, SI reduced those abilities and the level of LTP/DEP. Moreover, there were higher couplings of both phase–amplitude and phase–phase in the EE group, and lower couplings of them in the SI group compared to that in the CON group. Western blot and immunofluorescence analysis showed that EE significantly enhanced the level of PSD-95, NR2B and DCX; however, SI reduced them but increased GABAARα1 and decreased DCX levels. The data suggests that the cognitive functions, synaptic plasticity, neurogenesis and neuronal oscillatory patterns were significantly impacted by housing environment via possibly changing the balance of excitatory and inhibitory synaptic density.

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Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AMPA:

A-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid

DEP:

Depotentiation

DG:

Dentate gyrus

EE:

Enriched environment

E/I:

Excitatory/inhibitory

fEPSP:

Field excitatory postsynaptic potential

HG:

High gamma

HRP:

Horseradish peroxidase

IT:

Initial training

LFPs:

Local field potentials

LFS:

Low-frequency afferent stimulation

LG:

Low gamma

LTD:

Long-term depression

LTP:

Long term potentiation

MWM:

Morris water maze

MI:

Modulation index

NMDAR:

N-Methyl-d-aspartic acid receptor

PAC:

Phase–amplitude coupling

PLV:

Phase locking value

PP:

Perforant pathway

PPC:

Phase–phase coupling

PSD:

Power spectrum density

PSD-95:

Postsynaptic density protein 95

PVDF:

Poly vinylidene fluoride

RET:

Reversal exploring test

RI:

Recognition index

RT:

Reversal training

SET:

Space exploring test

SI:

Social isolation

SYP:

Synaptophysin

TBS:

Theta burst stimulation

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Funding

This work was supported by grants from the National Natural Science Foundation of China (Grant No. 31771148, 31900733), 111 Project (Grant No. B08011), China Postdoctoral Science Foundation (Grant No. 2019M651012) and the Applied Basic Research Programs of Science and Technology Commission Foundation of Tianjin (Grant No. 18JCYBJC27400).

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Author notes

  1. Hui Wang and Xiaxia Xu have contributed equally to this work.

Authors and Affiliations

  1. College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, People’s Republic of China

    Hui Wang, Xiaxia Xu, Xinxin Xu & Tao Zhang

  2. School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China

    Jing Gao

  3. School of Mathematical Sciences, Nankai University, Tianjin, 300071, People’s Republic of China

    Hui Wang

Authors
  1. Hui Wang
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  2. Xiaxia Xu
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  3. Xinxin Xu
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  4. Jing Gao
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  5. Tao Zhang
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Contributions

Hui Wang, Xiaxia Xu and Tao Zhang conceived and designed the experiment; Hui Wang, Xiaxia Xu, Xinxin Xu and Jing Gao performed the experiments and analyzed the data; and Hui Wang and Tao Zhang wrote and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Tao Zhang.

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We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

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Not applicable.

Ethics Approval and Consent to Participate

All procedures were carried out according to the NIH Guide for the Care and Use of Laboratory Animals and approved by the Ethical Commission at Nankai University (20160004).

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Wang, H., Xu, X., Xu, X. et al. Enriched Environment and Social Isolation Affect Cognition Ability via Altering Excitatory and Inhibitory Synaptic Density in Mice Hippocampus. Neurochem Res 45, 2417–2432 (2020). https://doi.org/10.1007/s11064-020-03102-2

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