Regulation of behaviour by the nuclear receptor TLX

J. D. O'Leary, O. F. O'Leary, J. F. Cryan, Y. M. Nolan

The orphan nuclear receptor Tlx (Nr2e1) is a key regulator of both embryonic and adult hippocampal neurogenesis. Several different mouse models have been developed which target Tlx in vivo including spontaneous deletion models (from birth) and targeted and conditional knockouts. Although some conflicting findings have been reported, for the most part studies have demonstrated that Tlx is important in regulating the processes that underlie neurogenesis, spatial learning, anxiety-like behaviour and interestingly, aggression. More recent data has demonstrated that disrupting Tlx during early life induces hyperactivity and has also shown that Tlx plays a role in emotional regulation. Moreover, there are sex and age-related differences in some behaviours in Tlx knockout mice during adolescence and adulthood. Here, we discuss the role of Tlx in motor, cognitive, aggressive and anxiety-related behaviours during adolescence and adulthood. We examine current evidence in the literature which provides insight into Tlx during neurodevelopment, and offer our thoughts on the function of Tlx in brain and behaviour. We further hypothesise that Tlx is a key target in understanding the emergence of neurobiological disorders during adolescence and early adulthood.