I Technical set up and procedures refinement inherent to specific research, as well as further exploitation for future research (see details in technical report)
1. Engineering of targeted deletion in space and developmental time
2. Set up of behavior room and positive symptoms test procedures and analyses (including self-motion analyses)
3. Refinement of specific immunohistochemistry procedures
II Overview of the research results (see details in technical report)
Our first result was to verify that conditional mutant presented a significant increase in positive symptoms at postnatal day P30 (such as exemplify by hyperlocomotion) compared to control mice. Once this established, we went on to test two different focal mutants resulting from targeted injection either the (1) frontal cortex or (2) the striatum. We then used immunohistochemistry methods with the goal to establish the accuracy of the erbb4 deletion in targeted cells, as well as their effect on the local network. However, we encounter strong caveats with this method and had to spend a considerable amount of time to refine our primary and secondary antigen combination, as well microscopy procedures. While we confirm accurate deletion at P30, we did not observe any further impact of the deletion on either the local network or the behavioral phenotype of either mutant, thus invalidating our original hypothesis. We then moved on to test local dopamine levels with microdyalisis. While we observed a significant increase in dopamine levels in conditional mutant, we did not replicate this result in focal mutants. Because of the covid crisis our access to animal facilities was strongly reduce, therefore prevented us to explore further these discrepancies with PET-scan and investigate whether our original hypothesis was truly invalidated and why. However, this situation provided us with extra-time to develop new computational methods to further investigate our behavioral results, specifically representations of velocity. This research revealed itself to be fertile and led us to discover a new type of velocity conjunctive coding, combining representation of both angular and linear velocity in normal subjects. We further tested this type of coding in other data set that we had access to, specifically a data set that the grant recipient had collected during her PhD. This discovery led to a very fruitful collaboration with the International School for Advanced Studies (SISSA) in Trieste.
III Exploitation and dissemination of the research results
As mentioned above, the MSCA was essential in establishing new methods at the University of Oslo. These methods formed the cornerstone of successful grant proposals that allowed the MSCA recipient to become an independent group leader at the University of Oslo. Intermediate results were regularly presented at internal labmeeting, seminars and institute retreat, where they were discussed with scientific assemblies of diverse size ranging from the core group (5-10 researchers) to >150 researchers belonging to the institute. Some of the results were also presented at the bi-annual meeting of the Federation of European neuroscience societies (FENS) regrouping over 5000 participants, as well as to the COSYNE meeting in Colorado (US). The recipient of the grant was also invited to present these results to multiple talks, including talks given to Queens Mary College (London, UK), The Technion (Haifa, Israel), SISSA (Trieste, Italy), NCMM (Oslo, Norway) and the university of Tsukuba (Japan). Most of these talks were given online because of the COVID restrictions. The manuscript covering part of the results obtain thanks to the MSCA funding was just officially accepted by Nature Communication.
