ADHDLightUp · Circuit-based deconstruction of Attention deficit and Hyperactive disorder with optogenetic Light control

Circuit-based deconstruction of Attention deficit and Hyperactive disorder with optogenetic Light control

Attention-deficit/hyperactivity disorder (ADHD) like many other mental illnesses probably results from a combination of genetic and developmental factors pointing at abnormalities in brain monoamines (MA) that include dopamine, serotonine and noradrenaline. Imaging studies in ADHD patients also indicate deficits in activity of various brain regions including the prefrontal cortex (PFC) and basal ganglia (BG). The mechanisms by which PFC and BG dysfunctions are triggered, and can be corrected with MA-based treatment are unknown. Although there is a consistent frontal hypoactivity detected in ADHD, some variations are seen amongst executive processes including attention or impulse control, in which MA have specific functions. Besides, the limited spatial resolution of brain imaging does not allow to detect certain subregions or discriminate neuronal subpopulations. In order to identify brain network impairments in ADHD, we need models to further dissect frontal dysfunctions looking at MA signaling, cell excitability and behavioral correlates of activity in identified neurons. The goal of the ADHD LightUp project was to untangle brain circuits involved in a novel mouse model of ADHD, which fulfills the major criteria reflecting human condition, showing MA involvement. Innovative approaches have been chosen to accomplish this challenge that include transgenesis, opto- and chemo-genetics, and in vivo measurement of neuronal activity in translational behavioral tasks assessing attention and impulsivity. Importantly, while the most common medication using psychotimulants has proven the best efficiency, it has also been shown to affect children growth and their adult mental health highlighting the urge for alternatives. The model developed here and the multidisciplinary experimental approach that was chosen aimed to provide new insights in ADHD ætiology and will allow to develop new concepts and/or targets for therapeutic alternatives further based on the manipulation of neurons activity to reverse or attenuate ADHD symptoms.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз