PT  - JOURNAL ARTICLE
AU  - Pavel Prosselkov
AU  - Qi Zhang
AU  - Hiromichi Goto
AU  - Denis Polygalov
AU  - Thomas J. McHugh
AU  - Shigeyoshi Itohara
TI  - Behavior Variability of a Conditional Gene Knockout Mouse as a Measure of Subtle Phenotypic Trait Expression. The Case of Mouse Executive Function Distortion
AID  - 10.1101/229856
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 229856
4099  - http://biorxiv.org/content/early/2018/01/13/229856.short
4100  - http://biorxiv.org/content/early/2018/01/13/229856.full
AB  - 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 (1). 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.