Periodic Reporting for period 2 - EvolutioNeuroCircuit (Cellular and genetic bases of neural circuits evolution)
Berichtszeitraum: 2020-09-01 bis 2022-02-28
Although as neuroscientists we are learning more each day about how brains work, we still know relatively little about how they evolve. This is a fundamental questions in biology and neuroscience. By understanding how the neural circuits inside brains change during evolutionary time, thus generating different behaviours, we might learn how to modify neural circuits in subtle ways, for example during diseases, it will also offer us a window as to how our own brain became the sophisticated machine it is today. However, this is an extremely hard question to address. Understanding how any brain works requires sophisticated methods and many years, to learn about how brains evolve we need to examine the neural circuits of different species with different behaviours, and determine how their circuits changed. To simplify this problem we are using as a model the simpler brain of fly (Drosophila) larva. We have chosen different fly species whose larvae have different behaviours towards odours, this is important for the survival of the larvae in the different environments where they live. We take a multidisciplinary approach where we use chemistry to understand the nature of the odours that larvae smell, physics to build microscopes to study the behaviour of the larvae, as well as to observe how their neurons function, we employ genetics to modify the genes of different species, we also make use of powerful computers and microscopes to be able to reconstruct every detail in the brain of these species, looking for differences that would explain their different behaviours. Eventually, we would like to understand how genes within neurons change the way they function and connect to each other to produce animals with different behaviours.
From a technical point of view we have put together a lot of equipment to be able to address the question of how neural circuits evolve. For example, together with our collaborators we contributed to the development of more powerful microscopy techniques (Janiak et al. Nature Communications, 2022) as well as novel machine designs to study the behaviour of small animals, such as the fly larvae (Cano-Ferrer et al., in prep). We have also set-up in the lab advance chemical analysis methods to study the environment where the fly and larvae we study live.
We also published results on how olfactory systems evolve by reconstructing the evolutionary path of a family of olfactory receptors (Prieto-Godino et al. eLife, 2021). Another publication focused how brains can evolve by preventing the normal death of neurons that occurs in every brain during development (Prieto-Godino et al. Science Advances, 2019). We also investigated and published work on how neural circuits evolve through regulation of splicing programmes (a molecular machinery that enables cells to generate different proteins out of the same genes) (Torres-Mendez et al. Science Advances, 2022).
In addition to this, we were able to image every neuron and every connection between them, synapses, in the brain of one fly species, and we have been comparing at this very high resolution the brain circuits of this species with those of a different species for which a brain map had been generated before, this approach is called comparative connectomics, and is very new. Based on our results from the comparative connectomics, we have begun building computational models of how information in processed in the brain of different species. To validate these models, we have been employing genetic engineering to visualise the neurons of different species. With these genetic tools, and the powerful microscopes we built, we are using advanced volumetric imaging methods to visualise the activity of different neurons in the circuit across species, testing predictions from our models. We are also studying which genes are being expressed in each of the neurons of the brain of different species. We are now looking at how differences in the genes that are expressed can explain differences in how neurons function and generate different behaviours. We have also introduced across species genetic tools that enable us to remotely activate and inactivate specific neurons to understand their role in the behaviour of the different species.
Finally, during the early stages of the covid pandemic when the lab remained closed, we took part in the efforts to control the pandemic, including participation in programmes to develop and implement testing, and we published a paper revising open access approaches that could help alleviate the burden that that covid-19 imposed on global health systems (Chagas et al. PLoS Biology, 2020).
We also published results on how olfactory systems evolve by reconstructing the evolutionary path of a family of olfactory receptors (Prieto-Godino et al. eLife, 2021). Another publication focused how brains can evolve by preventing the normal death of neurons that occurs in every brain during development (Prieto-Godino et al. Science Advances, 2019). We also investigated and published work on how neural circuits evolve through regulation of splicing programmes (a molecular machinery that enables cells to generate different proteins out of the same genes) (Torres-Mendez et al. Science Advances, 2022).
In addition to this, we were able to image every neuron and every connection between them, synapses, in the brain of one fly species, and we have been comparing at this very high resolution the brain circuits of this species with those of a different species for which a brain map had been generated before, this approach is called comparative connectomics, and is very new. Based on our results from the comparative connectomics, we have begun building computational models of how information in processed in the brain of different species. To validate these models, we have been employing genetic engineering to visualise the neurons of different species. With these genetic tools, and the powerful microscopes we built, we are using advanced volumetric imaging methods to visualise the activity of different neurons in the circuit across species, testing predictions from our models. We are also studying which genes are being expressed in each of the neurons of the brain of different species. We are now looking at how differences in the genes that are expressed can explain differences in how neurons function and generate different behaviours. We have also introduced across species genetic tools that enable us to remotely activate and inactivate specific neurons to understand their role in the behaviour of the different species.
Finally, during the early stages of the covid pandemic when the lab remained closed, we took part in the efforts to control the pandemic, including participation in programmes to develop and implement testing, and we published a paper revising open access approaches that could help alleviate the burden that that covid-19 imposed on global health systems (Chagas et al. PLoS Biology, 2020).
We have already learnt a lot of new things about how brains evolve, which elements tend to remain conserved and which ones change more between species. In the future, we will continue to show how these differences affect behaviour, and which are the genes mediating this evolutionary change.