Genetic background determines synaptic phenotypes in Arid1b-mutant mice

Hyosang Kim; Eunjoon Kim

doi:10.3389/fpsyt.2023.1341348

Genetic background determines synaptic phenotypes in Arid1b-mutant mice

Front Psychiatry. 2024 Mar 7:14:1341348. doi: 10.3389/fpsyt.2023.1341348. eCollection 2023.

Authors

Hyosang Kim¹, Eunjoon Kim^{1

2}

Affiliations

¹ Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
² Department of Biological Sciences, Korea Advanced Institute of Science and Technolgoy (KAIST), Daejeon, Republic of Korea.

Abstract

ARID1B, a chromatin remodeler, is strongly implicated in autism spectrum disorders (ASD). Two previous studies on Arid1b-mutant mice with the same exon 5 deletion in different genetic backgrounds revealed distinct synaptic phenotypes underlying the behavioral abnormalities: The first paper reported decreased inhibitory synaptic transmission in layer 5 pyramidal neurons in the medial prefrontal cortex (mPFC) region of the heterozygous Arid1b-mutant (Arid1b^+/-) brain without changes in excitatory synaptic transmission. In the second paper, in contrast, we did not observe any inhibitory synaptic change in layer 5 mPFC pyramidal neurons, but instead saw decreased excitatory synaptic transmission in layer 2/3 mPFC pyramidal neurons without any inhibitory synaptic change. In the present report, we show that when we changed the genetic background of Arid1b^+/- mice from C57BL/6 N to C57BL/6 J, to mimic the mutant mice of the first paper, we observed both the decreased inhibitory synaptic transmission in layer 5 mPFC pyramidal neurons reported in the first paper, and the decreased excitatory synaptic transmission in mPFC layer 2/3 pyramidal neurons reported in the second paper. These results suggest that genetic background can be a key determinant of the inhibitory synaptic phenotype in Arid1b-mutant mice while having minimal effects on the excitatory synaptic phenotype.

Keywords: ARID1B mutation; genetic background; miniature excitatory postsynaptic currents; miniature inhibitory postsynaptic currents; synaptic phenotype.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Institute for Basic Science (IBS-R002-D1 to EK).