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Genetics and function of neuronal circuits controlling goal oriented movements

Periodic Reporting for period 3 - Space and Motion (Genetics and function of neuronal circuits controlling goal oriented movements)

Reporting period: 2019-01-01 to 2020-06-30

Reaching for a cup of coffee or a pen on the desk as well as any object in our surrounding is a simple but fundamental ability that we all share and that, to a large extent, we perform effortlessly. Conditions that impair our motor abilities and impact on such basic motor skills put tremendous strain on the life of individuals. Albeit apparently simple, these actions are composed by multiple simpler steps that range from the cognitive endeavour of choosing a particular target for our actions, to that of coordinating a large number of muscles to produce a final movement that allows us to interact with the target of interest. Our work aims at understanding the neural encoding of such target directed actions with particular focus on the encoding of their metric (i.e. the direction of these movements). To this aim we focus our work on mice and we have chosen to analyse the neural underpinning of target directed head movements as these can be seen as the ethological equivalent of primates’ hand movements. We want to understand what brain networks are involved in the planning and executions of such actions and how the metric of these actions is encoded. Furthermore, we want to understand what neuronal populations are implicated in these processes and define their genetic identity.
We have successfully put in place a team for the project consisting of an engineer and three postdocs. We have made excellent progress on all these aspects during the first half of this award. In particular, we have generated the tools necessary to dissect the networks involved in the generation of target directed actions (Ciabatti et al., Cell 2017) and have defined the neuronal underpinning of the encoding of the metric of these actions (Wilson et al., Curr. Biol 2018). We are currently working in defining the genetic signatures of the neural population involved.
Multiple aspects of our project pushed the field way beyond the state of the art. This is particularly evident both in Wilson et al., 2018 as well as in Ciabatti et al., 2017. In the former we developed a completely novel method for tracking motion in 3d using a full sensor based approach. For the latter, the development of Self Inactivating Rabies allows, for the first time, the functional manipulation of neural networks without any time constraints. These works pave the way to the genetic dissection of brain wide circuit for targeted head motion. By the end of the project we aim to achieve a fairly complete genetic dissection of the collicular populations involved in the control of the metric of head motion.