How we experience the world is fundamental to survival and guides our behavior from completing a simple motor task to forming relationships. Perhaps unsurprisingly, the inability to filter out sensory information, a function termed sensorimotor gating, is an early and transversal endophenotype for diverse neuropsychiatric disorders. Nevertheless, research on the mechanisms linking maladaptive information processing and psychopathology is surprisingly lacking. According to epidemiological data, prenatal cannabis exposure (PCE) is a predictive risk factor for sensorimotor gating deficits. Notably, a rat model of PCE was able to (1) show that only preadolescent males display impaired sensorimotor gating functions upon subsequent “hits” (e.g. acute stress), and (2) associate this at-risk endophenotype with aberrant dopamine (DA) signalling in the mesolimbic pathway, which stretches from the ventral tegmental area (VTA) to the nucleus accumbens shell (NAcS). Remarkably, females do not show any of these alterations. One proposed gate towards these sex-dependent vulnerable and resilient phenotypes is the locus coeruleus (LC), the major source of noradrenaline (NA) in the brain and a key regulator of the stress response. Indeed, the LC, besides being a sexually dimorphic nucleus, is known to innervate the VTA and influence the mesolimbic DA pathway, including transmission in the NAcS. Nevertheless, the implication of LC→VTA NA inputs in the context of sensorimotor gating has never been investigated. The current project proposes to employ state-of-the-art neurobiological techniques to test with unprecedented precision and resolution the overarching hypothesis that the LC NA system exerts a sex-dependent regulatory role onto VTA DA functioning in the context of sensory information processing in health and disease (i.e. PCE, stress). Identifying biased NA mechanisms could be exploited to restore deranged developmental trajectories during sensitive windows of neurodevelopment.

Currently, there is a vast amount of research activity taking place into the development of new materials having unconventional properties and the respective technologies have been opening new eras through various applications for society. This new generation of materials, or metamaterials, have led to interesting physical properties previously thought impossible such as cloaking, negative refraction and materials that contract when heated. Most of those properties are realised in the dynamic response of the material. However, in these dynamic processes uncertainty remains as to whether these metamaterials undergo feasible deformations, remaining intact. Research into the latter is limited. Understanding this phenomenon is important in developing new metamaterials. Additionally it is crucial, for example, in larger structures such as multi-span bridges, pipelines and skyscrapers exposed to earthquakes and terrorist attacks, regularly faced in Europe and their effects can be catastrophic to human life. To accomplish this research, a significant multidisciplinary effort is required from applied mathematicians, engineers, computer scientists and industrialists closely collaborating towards this one goal. This timely project has two aims: (i) to create a well-rounded researcher capable of interacting with engineers and industrialists and (ii) this should be executed through the research into this area or more specifically the dynamic failure propagation in structured media under various loading conditions. This will be achieved through establishing an international and multidisciplinary long-standing collaboration between the European Fellow (EF), who is an applied mathematician, academic partner UniCA and industrial partner ES. Through this, a unique research environment will be created offering essential training not possible at the EF’s home institute, creating new skills that will complement the EF’s existing strengths to enable objectives (i) and (ii).