AUTHOR=Kim Hyosang , Kim Eunjoon 

TITLE=Genetic background determines synaptic phenotypes in Arid1b-mutant mice

JOURNAL=Frontiers in Psychiatry

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1341348

DOI=10.3389/fpsyt.2023.1341348

ISSN=1664-0640

ABSTRACT=<p>ARID1B, a chromatin remodeler, is strongly implicated in autism spectrum disorders (ASD). Two previous studies on <italic>Arid1b</italic>-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 <italic>Arid1b</italic>-mutant (<italic>Arid1b</italic><sup>+/−</sup>) 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 <italic>Arid1b</italic><sup>+/−</sup> 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 <italic>Arid1b</italic>-mutant mice while having minimal effects on the excitatory synaptic phenotype.</p>