Overexpression of neuronal K+–Cl co-transporter enhances dendritic spine plasticity and motor learning

  • Kayo Nakamura
  • Andrew John Moorhouse
  • Dennis Lawrence Cheung
  • Kei Eto
  • Ikuko Takeda
  • Paul Wiers Rozenbroek
  • Junichi NabekuraEmail author
Original Paper


The neuronal K+–Cl cotransporter KCC2 maintains a low intracellular Cl concentration and facilitates hyperpolarizing GABAA receptor responses. KCC2 also plays a separate role in stabilizing and enhancing dendritic spines in the developing nervous system. Using a conditional transgenic mouse strategy, we examined whether overexpression of KCC2 enhances dendritic spines in the adult nervous system and characterized the effects on spine dynamics in the motor cortex in vivo during rotarod training. Mice overexpressing KCC2 showed significantly increased spine density in the apical dendrites of layer V pyramidal neurons, measured in vivo using two-photon imaging. During modest accelerated rotarod training, mice overexpressing KCC2 displayed enhanced spine formation rates, greater balancing skill at higher rotarod speeds and a faster rate of learning in this ability. Our results demonstrate that KCC2 enhances spine density and dynamics in the adult nervous system and suggest that KCC2 may play a role in experience-dependent synaptic plasticity.


Two-photon microscopy In vivo Motor learning KCC2 Synaptic plasticity 



We thank Ms. Tatsuko Oba for the support of animal maintenance and preparation and Dr. Miho Watanabe at Hamamatsu Medical University for a useful suggestion for the analysis of KCC2 expression and staining.

Author contributions

KN, DLC, PWR, KE and IT conducted experiments; KN, AJM and JN wrote the paper; AJM and JN conceived the study. All authors approved the final version of the manuscript.


This study was supported by JSPS KAKENHI grant no. JP17H01530 and JP25253017 to JN. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants. All animal experiments were approved by the Okazaki Institutional Animal Care and Use Committee or by the UNSW Sydney Animal Care and Ethics Committee.


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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Homeostatic Development, Department of Fundamental NeuroscienceNational Institutes for Physiological SciencesOkazakiJapan
  2. 2.Department of Physiological SciencesSokendaiHayamaJapan
  3. 3.Department of Physiology, School of Medical SciencesUniversity of New South WalesSydneyAustralia

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