The nucleus incertus (NI) of the pontine periventricular grey consists of GABAergic neurons with long-range ascending projections to forebrain. Efferent and afferent connections of the rat NI suggest a role in ‘behavioural planning, habenular function, hippocampal/cortical activity in attention/memory, and in oculomotor control’ . The NI is a site of corticotropin releasing-factor (CRF) action, and forms a neural network positioned to modulate arousal and stress responses and the de/synchronization of hippocampal theta rhythm , a prominent oscillatory activity (4-12 Hz) in the electroencephalograph (EEG) observed during goal-oriented exploration and memory processes. Importantly, NI neurons are also a primary source of the neuropeptide, relaxin-3, which acts via the Gi-protein-coupled receptor, RXFP3. Past research has identified a role for relaxin-3/RXFP3 neural networks in motivated feeding, via modulation of hypothalamic areas, and reward behaviour via actions in limbic regions, in the rat and mouse (see [3-5]). Our more recent research suggests this neuropeptide is involved more broadly in regulating arousal and higher cognitive processes in the rat. Current data suggests the NI and relaxin-3 neural systems regulate behavioural state; and our findings on this integrative neural network will be reviewed, in particular recent findings on brain physiology and arousal processes using pharmacogenetic approaches, with implications for the therapeutic potential of relaxin-3/RXFP3.