Periodic Reporting for period 1 - FunStructure (Interdependence of functional and structural plasticity in cerebellar climbing fibers in health and disease)
Reporting period: 2019-07-01 to 2021-06-30
How neurons encode memory remains one of the current challenges of neuroscience. The cerebellum represents a valuable model area to investigate this, for instance because of its simple and modular structural organization and for the direct control of simple motor outputs. It is known that a combination of phenomena occurring at different sites of the circuit can contribute to encode memory. These are several forms of “activity-dependent plasticity” (i.e. changes in properties of neurons that are caused by their activity, representing a trace of previous events and experiences). Understanding these mechanisms and how they are altered in pathological conditions allows identifying and designing better intervention strategies to restore brain functions in brain diseases.
Specifically in this project we have investigated the role of one of the only two inputs of the cerebellum, known as “climbing fiber”. It is well known that it plays a crucial role in “instructing” the cerebellum on motor errors, and, by doing this, it fine-tunes the circuit. It has been, however, unknown whether this kind of fibers can significantly change their morphology based on their activity as other fibers can do in other brain areas, and whether this could contribute to encode memories. We have studied this possibility finding that they are actually able to change their structure based on their activity and we have provided first evidence suggesting that this may potentially affect the function of the circuit and that, therefore, this mechanism may contribute to encode memories. This is adding a new element in the complex group of mechanisms that allows the cerebellum to encode and store memories and the basis for a better understating of brain function and dysfunction.
Specifically in this project we have investigated the role of one of the only two inputs of the cerebellum, known as “climbing fiber”. It is well known that it plays a crucial role in “instructing” the cerebellum on motor errors, and, by doing this, it fine-tunes the circuit. It has been, however, unknown whether this kind of fibers can significantly change their morphology based on their activity as other fibers can do in other brain areas, and whether this could contribute to encode memories. We have studied this possibility finding that they are actually able to change their structure based on their activity and we have provided first evidence suggesting that this may potentially affect the function of the circuit and that, therefore, this mechanism may contribute to encode memories. This is adding a new element in the complex group of mechanisms that allows the cerebellum to encode and store memories and the basis for a better understating of brain function and dysfunction.
The electrical activity and morphology of cerebellar climbing fibers have been manipulated in vivo with viral vectors allowing the investigation of the morphological (structural) consequences of changes in their electrical activity as well as the functional consequences of changes in their structure. This allowed showing that cerebellar climbing fibers are able to change their structure based on their activity and this may potentially affect the function of the circuit contributing to encode memories.
These results have been presented to the scientific community at several neuroscience conferences (1 international and 2 national conferences), and are expected to be presented at several others. They will be published in peer-reviewed scientific journals (manuscript in preparation) and the data will be available online.
Topics closely related to this project have been disseminated to students and the general public through several invited talks and guest lectures and one peer-review outreach article (published both in Italian and English on the online outreach journal “AIRInforma” of the International Association of Italian Researcher AIRIcerca).
These results will be also exploited as starting point for further scientific projects.
These results have been presented to the scientific community at several neuroscience conferences (1 international and 2 national conferences), and are expected to be presented at several others. They will be published in peer-reviewed scientific journals (manuscript in preparation) and the data will be available online.
Topics closely related to this project have been disseminated to students and the general public through several invited talks and guest lectures and one peer-review outreach article (published both in Italian and English on the online outreach journal “AIRInforma” of the International Association of Italian Researcher AIRIcerca).
These results will be also exploited as starting point for further scientific projects.
So far it was believed that cerebellar climbing fibers can have only limited (if any) change in morphology due to changes in their electrical activity. Our results for the first time show that this kind of fibers can significantly change their morphology due to changes in their electrical activity and that these morphological changes can have functional consequences that may be relevant for the circuit function and, consequently, for memory formation. This is adding a new element in the complex group of mechanisms that allows the cerebellum to encode and store memories therefore contributing to the body of knowledge that is necessary to understand brain function and dysfunction.