Synaptic functions and their disruption in schizophrenia: From clinical evidence to synaptic optogenetics in an animal model

Proc Jpn Acad Ser B Phys Biol Sci. 2019;95(5):179-197. doi: 10.2183/pjab.95.014.

Abstract

The adult human brain consists of approximately a hundred billion neurons, which are connected via synapses. The pattern and strength of the synaptic connections are constantly changing (synaptic plasticity), and these changes are considered to underlie learning, memory, and personality. Many psychiatric disorders have been related to disturbances in synaptogenesis and subsequent plasticity. In this review, we summarize findings of synaptic disturbance and its involvement in the pathogenesis and/or pathophysiology of psychiatric disorders. We will focus on schizophrenia, because this condition has a high proven heritability, which offers more unambiguous insights into the biological origins of not only schizophrenia but also related psychiatric disorders. To demonstrate the involvement of synaptopathy in psychiatric disorders, we discuss what knowledge is missing at the circuits level, and what new technologies are needed to achieve a comprehensive understanding of synaptopathy in psychiatric disorders.

Keywords: AS-PaRac1; optogenetics; schizophrenia; synaptic integration; synaptopathy.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Brain / pathology
  • Humans
  • Optogenetics
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / genetics*
  • Schizophrenia / pathology*
  • Synapses / pathology*