PT  - JOURNAL ARTICLE
AU  - Pavel Prosselkov
AU  - Qi Zhang
AU  - Goto Hiromichi
AU  - Denis Polygalov
AU  - Thomas J. McHugh
AU  - Shigeyoshi Itohara
TI  - Molecular Correlate of Mouse Executive Function. Top-Down and Bottom-Up Information Flows Complementation by <em>Ntng</em> Gene Paralogs
AID  - 10.1101/139444
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 139444
4099  - http://biorxiv.org/content/early/2017/05/29/139444.short
4100  - http://biorxiv.org/content/early/2017/05/29/139444.full
AB  - Executive function (EF) is a regulatory construct of learning and a main characteristic of general cognitive abilities. Genetic variations underlying the architecture of cognitive phenotypes are likely to affect EF. Mice lacking one of Ntng gene paralogs, encoding the vertebrate brain-specific presynaptic Netrin-G proteins, exhibit prominent deficits in the EF control. Brain areas responsible for gating the bottom-up and top-down information flows differentially express Ntng1 and Ntng2, distinguishing neuronal circuits involved in perception and cognition. As a result, high and low cognitive demand tasks (HCD and LCD, respectively) modulate Ntng1 and Ntng2 associations either with attention and impulsivity (AI) or working memory (WM), in a complementary manner. During the LCD Ntng2-supported neuronal gating of AI and WM dominates over the Ntng1-associated circuits. This is reversed during the HCD, when the EF requires a larger contribution of cognitive control, supported by Ntng1, over the Ntng2 pathways. Since human NTNG orthologs have been reported to affect human IQ (1), and an array of neurological disorders (2), we believe that mouse Ntng gene paralogs serve an analogous role but influencing brain executive function.