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Enduring effects of juvenile social isolation on physiological properties of medium spiny neurons in nucleus accumbens

  • Xiao-Qin Zhang
  • Zhi-Peng Yu
  • Yu Ling
  • Qi-Qi Zhao
  • Zhong-Yu Zhang
  • Zheng-Chun Wang
  • Hao-Wei ShenEmail author
Original Investigation

Abstract

Rationale

Juvenile social isolation (SI) and neglect is associated with a wide range of psychiatric disorders. While dysfunction of the corticolimbic pathway is considered to link various abnormal behaviors in SI models of schizophrenia, the enduring effects of early social deprivation on physiological properties of medium spiny neurons (MSNs) in nucleus accumbens (NAc) are not well understood.

Objectives

This study investigated the impacts of juvenile SI on locomotor activity to methamphetamine (METH) and neurophysiological characteristics of MSNs in the core of NAc.

Methods

Socially isolated C57BL/6 mice experienced single housing for 4 weeks on postnatal day (PND) 21. The locomotor response to METH (1.0 mg/kg) was observed in both socially isolated and group-housed mice at PND 56. The effects of juvenile SI on the excitatory synaptic events in MSNs and the intrinsic excitability of MSNs in NAc core were investigated in other batches during PND 63–70.

Results

Socially isolated mice showed locomotor hypersensitivity to METH, although the expression of locomotor sensitization to METH in socially isolated mice was not different from group-housed mice. The recordings from MSNs of SI-reared mice exhibited higher frequency and smaller amplitude of miniature/spontaneous excitatory postsynaptic current than those from group-reared mice. Moreover, SI resulted in increased intrinsic excitability of MSNs in adult mice.

Conclusions

These results demonstrate neuronal hyperactivity in the NAc of socially isolated mice, which could contribute to locomotor hypersensitivity to METH. Furthermore, the findings indicate a biological link between early negative life events and the vulnerability to psychostimulant-induced psychosis in adulthood.

Keywords

Social isolation Locomotor activity Nucleus accumbens Neuronal excitability 

Abbreviations

SI

Social isolation

PND

Postnatal day

METH

Methamphetamine

MSNs

Medium spiny neurons

NAc

Nucleus accumbens

PPI

Pre-pulse inhibition

PFc

Prefrontal cortex

EPSCs

Excitatory postsynaptic currents

Notes

Acknowledgments

We thank Lan-Yuan Zhang for technical assistance and He-Jia Jang, Si-Yu Yang and Teng Wu for assistance with pilot experiments conducted during an undergraduate research internship. We appreciate Dr. C. Benjamin Naman (Ningbo University – China and University of California, San Diego – USA) for critical reading and linguistic editing of the manuscript.

Authors’ contributions

Xiao-Qin Zhang and Hao-Wei Shen designed the experiments. Xiao-Qin Zhang and Zhi-Peng Yu performed the electrophysiological experiments. Yu Ling and Qi-Qi Zhao performed behavioral experiments. Xiao-Qin Zhang and Zhong-Yu Zhang performed the data analysis. Xiao-Qin Zhang and Hao-Wei Shen wrote the manuscript.

Funding

This research was financially supported by the National Key R&D Program of China (Grant 2017YFC0803605), the Natural Science Foundation of China (Grant 31571094), the Natural Science Foundation of Ningbo (Grant 2018A610289), and the K. C. Wong Magna Fund in Ningbo University.

The above funds paid for expenses related to research including supplies and personnel costs.

Compliance with ethical standards

All procedures were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and these were approved by the Animal Care and Use Committees of Ningbo University, China.

Conflict of interest

All authors declare that they have no conflicts of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Xiao-Qin Zhang
    • 1
  • Zhi-Peng Yu
    • 1
  • Yu Ling
    • 1
  • Qi-Qi Zhao
    • 1
  • Zhong-Yu Zhang
    • 2
  • Zheng-Chun Wang
    • 1
  • Hao-Wei Shen
    • 1
    Email author
  1. 1.Department of PharmacologyMedical School of Ningbo UniversityZhejiangChina
  2. 2.Department of Pharmacology, School of Basic Medical SciencesPeking UniversityBeijingChina

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