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Behavior variability of a conditional gene knockout mouse as a measure of subtle phenotypic trait expression. The case of mouse brain executive function distortion

By Pavel Prosselkov, Qi Zhang, Hiromichi Goto, Denis Polygalov, Thomas J. McHugh, Shigeyoshi Itohara

Posted 08 Dec 2017
bioRxiv DOI: 10.1101/229856

Task learning relies on brain executive function (EF), the construct of controlling and coordinating behavior under the everlasting flow of environmental changes. We have previously shown, that a complete knockout of a vertebrate brain-specific pair of gene paralogs (Ntng1/2) distorts the mouse EF, making behavior less predictable (more variable) via the affected working memory and attention. In the current study, conditionally targeting either serotonin transporter (5-HTT) or Emx1-expressing neurons, we show that the cell type-specific ablation of Ntng1 within the excitatory circuits of either cortex or thalamus does not have a profound impact on the EF but rather affects its certain modalities, i.e. impulsivity and/or selective attention, modulated by cognitive demand. Several mice of both conditional genotypes simultaneously occupy either top or bottom parameter-specific behavioral ranks, indicative of a subject-unique antagonistic either proficit or deficit of function within the same behavior. Employing genotype-attributable behavior variability as a phenotypic trait, we deduce, that Ntng1-parsed excitatory pathways contribute but do not fully reconstitute the attention-impulsivity phenotypes, associated with the mouse EF deficit. However, complete knockdown of Ntng1/2, and associated with it behavior variability, explains the deficit of executive function and task learning.

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