RT Journal Article SR Electronic T1 MOLECULAR CORRELATE OF MOUSE EXECUTIVE FUNCTION. TOP-DOWN and BOTTOM-UP INFORMATION FLOWS COMPLEMENTATION by Ntng GENE PARALOGS JF bioRxiv FD Cold Spring Harbor Laboratory SP 139444 DO 10.1101/139444 A1 Pavel Prosselkov A1 Qi Zhang A1 Goto Hiromichi A1 Denis Polygalov A1 Thomas J. McHugh A1 Shigeyoshi Itohara YR 2017 UL http://biorxiv.org/content/early/2017/06/08/139444.abstract 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.