The action comprised 3 Key Objectives:
Key Objective 1 investigated activity-dependent plasticity in dopaminergic neurons in the olfactory bulb. Work on this Key Objective contributed to a paper showing key baseline structural and functional differences between olfactory bulb dopaminergic neurons born in embryonic development versus those born in adulthood (Galliano et al., eLife 2018
https://doi.org/10.7554/eLife.32373(odnośnik otworzy się w nowym oknie); associated Open Data:
http://dx.doi.org/10.5061/dryad.b5hg8d6(odnośnik otworzy się w nowym oknie)). A second paper then showed differential capacity for experience-dependent structural and functional plasticity in these dopaminergic sub-types (Galliano et al., Journal of Neuroscience 2021
https://doi.org/10.1523/JNEUROSCI.1606-20.2020(odnośnik otworzy się w nowym oknie); associated Open Data
http://doi.org/doi:10.18742/RDM01-757(odnośnik otworzy się w nowym oknie)). Core work on this Key Objective was the doctoral project of Candida Tufo, who obtained her PhD in June 2022, contributed to our 2021 paper, and first-authored a high-impact review on olfactory bulb development (Tufo et al., Development 2022
https://doi.org/10.1242/dev.200210(odnośnik otworzy się w nowym oknie)). Dr Tufo’s investigation of activity-dependent plasticity in adult-born olfactory bulb dopaminergic neurons found, somewhat surprisingly, that immature adult-generated cells were not more plastic than their older, pre-existing neighbours. They were, however, distinguished by functional differences associated with their immature status. This work is currently being prepared for submission.
Key Objective 2 addressed the olfactory sensory response properties of adult-born olfactory bulb dopaminergic cells. Data collection on this Key Objective ran right up to the termination of the action, and is currently undergoing analysis for submission in 2023.
Key Objective 3 was slightly re-focused given the unexpected results obtained in Key Objective 1, as is entirely appropriate for a basic scientific project of this duration. Remaining fully in line with the overall aims of the action, we established new, state-of-the-art techniques for examining multi-omic plasticity in dopaminergic neurons (Lipovsek et al., Star Protocols 2020
https://doi.org/10.1016/j.xpro.2020.100146(odnośnik otworzy się w nowym oknie); associated Open Data
http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE151709(odnośnik otworzy się w nowym oknie)) found evidence for molecular-level plasticity in this cell type (Byrne et al., European Journal of Neuroscience 2022
https://doi.org/10.1111/ejn.15684(odnośnik otworzy się w nowym oknie); associated Open Data
https://doi.org/10.18742/19698187.v1(odnośnik otworzy się w nowym oknie)) and are currently analysing, for forthcoming publication, exciting data linking plasticity in gene expression to neuronal function at the single-cell level. This work also contributed to a highly cited publication which - in a great demonstration of how ERC-funded basic research can tackle previously unanticipated translational problems - investigated the potential mechanisms underlying anosmia in COVID-19 (Brann et al., Science Advances 2020
https://doi.org/10.1126/sciadv.abc5801(odnośnik otworzy się w nowym oknie); associated Open Data
http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE151709(odnośnik otworzy się w nowym oknie)). Finally, work on Key Objective 3 also uncovered novel mechanisms by which neuronal circuits – including dopaminergic neurons – can change in response to naturally-occurring regeneration of sensory inputs (Browne et al. bioRxiv 2022
https://doi.org/10.1101/2022.06.09.493421(odnośnik otworzy się w nowym oknie)). We have harnessed the regenerative potential of the mammalian olfactory system to discover ways in which newly-grown inputs can re-connect with and drive functional information processing in their target circuits, and this will remain a key focus of our work going forward.
Throughout the action, we have disseminated our findings at the earliest possible opportunity to the widest possible audience. We have presented preliminary work at national and international conferences, and have deposited all manuscripts at first submission in the Open Access preprint server bioRxiv. Our peer-reviewed publications have all been immediate Gold Open Access, and the full raw datasets from our primary research publications have all been published and made publicly available (see links above) as per the Open Data Pilot. We have also taken opportunities to publicise our findings via press releases, interviews, and social media.
