Periodic Reporting for period 1 - Syn2Psy (Synaptic Dysfunction in Neuropsychiatric Disorders)
Reporting period: 2019-03-01 to 2021-02-28
The objective of Syn2Psy is to provide high-level Ph.D. training for 14 early stage researchers (ESRs) to answer three critical questions: 1) What are the synaptic defects at the basis of neuropsychiatric disorders? 2) Which are the neuronal circuits that are disrupted, and may be targets for therapies? 3) How and when can we modulate the course of disease? Syn2Psy combines strong scientific with complementary know-how from the non-academic sector, and network-wide actions on scientific and complementary soft skills, to train a new generation of high achieving ESRs and provide them with the transferable skills necessary for thriving careers in a flourishing area. Industrial partners Lundbeck, Eurotrials and ZEISS provide experience on drug, clinical trials and technology development, the Coimbra University Hospital will expose the students to clinical research, while the clinic for child development PIN and the Marionet theatre company offer training in societal awareness and outreach. The excellent basic scientific knowledge and diverse skills acquired by ESRs will enhance their employment prospects in both the academic and non-academic sectors, and their scientific contributions will inform novel therapeutic approaches for alleviating this leading cause of disability worldwide.
To dissect nanostructural changes in synapse dynamics in models of neuropsychiatric disorders and to explore the mechanisms underlying excitation/inhibition (E/I) imbalance in models of neuropsychiatric disease and to monitor E/I balance at the population level, Syn2Psy ESRs are focusing on the identification of the link between synaptic nanoscale alterations and behavioural defects in animal and human models of Shank3-related Autism Spectrum Disorder (ASD); on the characterization of cortical E/I imbalance in vivo in models of synaptic dysfunction using mesoscopic methods; on the identification of defects in single N-methyl-D-aspartate (NMDA) receptor dynamics in Psychosis; on the identification of presynaptic defects and alterations in glutamate receptor dynamics in Fragile X Syndrome (FXS); on the depiction of synapses and functional networks in a new paradigm to model Down’s Syndrome (DS); and on the characterization of the synaptic and neural correlates of spatial memory deficits in a glycine receptor knockout model of ASD.
Finally, Syn2Psy ESRs are focusing on the study of the therapeutic potential of the endocannabinoid system in an Autism Spectrum Disorder (ASD) model; on the identification of aberrant synaptic mRNA translation as a point of convergence for multiple genetic causes of ASD/ID; on the establishment of the impact of the corticotropic releasing hormone system on Schizophrenia (SCZ)- and ASD- related endophenotype; on the identification of circuit deficits associated with ASD; as well as on the identification of the role of the excitation/ inhibition (E/I) imbalance in the corticothalamic system in the development of neuropsychiatric disorders.