Excitatory and inhibitory synaptic dysfunction in mania: An emerging hypothesis from animal model studies

Yeunkum Lee, Yinhua Zhang, Shinhyun Kim, Kihoon Han

Research output: Contribution to journalReview articlepeer-review

44 Citations (Scopus)


Bipolar disorder (BD) is a common psychiatric disorder characterized by recurrent mood swings between depression and mania, and is associated with high treatment costs. The existence of manic episodes is the defining feature of BD, during which period, patients experience extreme elevation in activity, energy, and mood, with changes in sleep patterns that together severely impair their ability to function in daily life. Despite some limitations in recapitulating the complex features of human disease, several rodent models of mania have been generated and characterized, which have provided important insights toward understanding its underlying pathogenic mechanisms. Among the mechanisms, neuronal excitatory and inhibitory (E/I) synaptic dysfunction in some brain regions, including the frontal cortex, hippocampus, and striatum, is an emerging hypothesis explaining mania. In this review, we highlight recent studies of rodent manic models having impairments in the E/I synaptic development and function. We also summarize the molecular and functional changes of E/I synapses by some mood stabilizers that may contribute to the therapeutic efficacy of drugs. Furthermore, we discuss potential future directions in the study of this emerging hypothesis to better connect the outcomes of basic research to the treatment of patients with this devastating mental illness.

Original languageEnglish
Article number12
JournalExperimental and Molecular Medicine
Issue number4
Publication statusPublished - 2018 Apr 1

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government Ministry of Science, ICT & Future Planning (MISP) (NRF-2015R1C1A1A01052794), by the Brain Research Program through the NRF funded by the MISP (NRF-2015M3C7A1028790), by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (HI16C0090), and by a Korea University grant.

Publisher Copyright:
© 2018 The Author(s).

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry


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