INSTINCT

Instinctive or innate behaviours such as eating, social interaction, mating, parental care, defence and aggression, are fundamental for survival and reproduction. Innate behaviours do not need to be learned, are encoded by developmentally hard-wired subcortical circuits and are conserved across mammalian species. In this highly ambitious synergistic research programme, which builds on our track record of discoveries, our aim is to deliver a step-change in the understanding of mammalian innate behaviour. INSTINCT partners have developed technological approaches and defined distinct neural signatures of innate behaviour (Branco). Our pioneering studies showed that genetic disruption of hypothalamic circuits which defend against starvation, increases the drive to eat (hyperphagia) and causes obesity in humans (Farooqi). Uniquely, by modelling human genetic disorders in mice, Xu and Farooqi identified causal mechanisms underlying anxiety, aggression, reduced socialisation and postpartum depression. Now, by working together, across scientific disciplines, we will: 1. Identify new genetic causes of disordered human innate behaviour by studying people with hyperphagic obesity and anxiety/aggression/autistic spectrum disorder from childhood. We will develop and phenotype mouse models of these conditions, using leading-edge technologies to measure behaviour in naturalistic social settings. 2. Integrate state-of-the-art functional neuroimaging in humans and systems neuroscience approaches in mice, to define the neural basis of disordered innate behaviour. 3. Test how external stimuli such as smell and stress impact the brain and behaviour, building tools to permit synergistic studies in mice and humans. 4. Investigate how synaptic strength modulation in hard-wired circuits contributes to changes in behaviour and integrate multi-dimensional datasets to build computational models of mammalian innate behaviour.