This report corresponds to the final reporting period of the project (6 + 8 months extension). During this period the project has developed without major scientific deviations from the last reported plan and followed the original goals.
Aim 1 (100% completion). This aim was finished in year 2, as planned. We have successfully generated embryonically visually deprived mice by in utero bilateral enucleation in embryos (embBE). We exploited this animal model to check for neuroplastic compensatory mechanisms in the cortex and found that after embBE, the barrel field area in the primary somatosensory cortex (S1) is significantly expanded before sensory processing. Our work has demonstrated the existence of a novel mechanism that takes place in the perinatal thalamus and allows neuroplasticity of cortical territories to unfold upon input sensory loss (Moreno-Juan et al., 2017).
Aim 2 (100% completion). We defined the thalamic mechanisms derived from peripheral input loss that are involved in the plasticity of sensory cortical areas. Those mechanisms involved spontaneous activity patterns in the thalamus and an intra-thalamic communication among sensory-nuclei (Moreno-Juan et al., 2017). We have also determined the role of embryonic thalamic waves in the formation of sensory cortical maps (Anton-Bolaños et al., 2019) and cortico-thalamic circuits formation (Moreno-Juan et al., under second review eLife). During this period, we characterized the mechanisms involved in the integration of thalamic interneurons and the impact of their number modification in the sensory-deprived conditions. We found that blocking thalamic waves lead to an increase sensory of GABAergic interneurons in the visual (dLGN) thalamus, and thus perturbs the integration of interneurons in the visual system. This part of the project and results are being prepared for publication (Huerga et al.). We have also successfully overcome the difficulties mentioned in our last reporting period on the recordings of spontaneous activity in thalamus and cortex of non-anaesthetized new-born mice by combining meso-scale calcium imaging with extracellular recordings. These experiments yield promising results that we have already presented at international meetings (Society for Neuroscience Meeting, Chicago 2019; FENS 2020) and are going to be submitted for publication shortly (Guillamon-Vivancos et al.).
Aim 3 (100% completion). During the consecution of the project, and as written in the proposal, we successfully reprogrammed thalamic astrocytes in vitro and found that the origin of brain astrocytes determines the identity of the induced neurons they give rise. In this period, we have performed RNAseq analysis and single-cell sequencing analysis and found the signalling cascade by which this fate determination is achieved. This aim has been recently published in the journal Science Advances (Herrero-Navarro et al., 2021).
During the consecution the project, we have yielded a significant number of scientific peer reviewed papers (13 in total), some of them published in very high impact journals such as Science, Science Advances and Nature Communications, among others. We envisage at least 3 more high impact papers derived from this grant that are expected to be submitted shortly (Guillamón-Vivancos et al., in preparation, Moreno-Juan et al., in preparation and Huerga et al., in preparation). The successful competition of this project can be also measured by the number of invited talks to world-wide recognised meetings, awards received and mentoring derived.
Most significant achievements derived from the ERC-CoG grant:
1) Direct publications from the laboratory (in peer-reviewed journals, see in project publications)
2) Co-author publications from collaborations related to the project (in peer-reviewed journals, see in project publications)
3) Prizes and Awards
Alberto Sols award to the best publication in 2019
“Constantes y Vitales” Award to the best publication in Biomedicine in Spain 2019
Award to the Scientific Merit from the “Generalitat Valenciana” 2018
Joseph Altman prize in Developmental Neurobiology 2018
The IBRO-Kemali International Prize winner 2017
4) Invited Speaker to International Meetings, importantly: Janelia Conference in Neural Circuit Assembly (2020), Thalamocortical Gordon Research (2020), Cortical development Meeting (2020), FENS2020, EMBO Workshop Molecular Neurobiology (2020), EMBO Neural Guidance Cues Workshop (2019), EMBO conference on Cell Biology of the Neuron (2019), EMBL Symposium: Probing Neural Dynamics with Behavioural Genetics (2019), SPONT2018 (Co-organizer), ABCAM 'Programming and Reprogramming the Brain' (Munich, 2017); Brain Conference (Copenhagen, 2017); CSHL Meeting (New York, 2016); ISDN (Antibes, 2016), AXON2015 (Viena, 2015).
As a consequence of the productivity and visibility derived from the ERC CoG, I am a member of the program committee for the Spanish Society for Neuroscience (SENC) and I was in 2018 for the Federation of European Neuroscience Societies (FENS).
