Project description
Untangling the intertwined factors contributing to memory formation and loss
Neurons are dynamic cells whose structure and function are constantly changing. One of the key physiological properties of neurons that is modulated in many ways is excitability. This may be linked to structural changes in axonal morphology; further, both are related to learning and formation of memories. The EU-funded FunStructure project is manipulating axonal morphology and excitability in cerebellar brain slices and in vivo. Given that the cerebellum is critical to motor function and plays a role in both short- and long-term memory. Insight could shed light on plasticity in sickness and in health with applications in multiple sclerosis, memory loss conditions and more.
Objective
Modifications of the structure and intrinsic excitability of neurons (i.e. “structural plasticity” and “intrinsic plasticity”) have been proposed to contribute significantly in encoding memory in synergy with synaptic plasticity and have been shown to contribute to the pathogenesis of several diseases including multiple sclerosis (MS). However, it is still largely unclear how changes in intrinsic excitability affect structural plasticity and how this affects circuit function. A better understanding of this two-way interdependence is crucial to understand how brain circuits encode memory engrams and are affected by diseases. Here I propose to investigate the two sides of this function-structure relationship choosing cerebellar climbing fibers (CF) as a model. Using in vivo viral delivery in the inferior olive nucleus (where climbing fibers originate), electrophysiology, optogenetics and confocal microscopy I will modulate CF function or structure acutely in slice or chronically in vivo and analyze the corresponding effect on CF morphology or physiology, respectively. I will use previously developed viral constructs to silence the expression of the growth-associated protein 43 (GAP-43) or voltage-gated sodium channels to induce structural modifications or a reduction of excitability in CFs, respectively; I will also use optogenetics to specifically stimulate transduced CFs in slice and a recently established conditional knockout mouse for SK2-type calcium-gated potassium channels to increase CF excitability. In order to investigate how CF function and structure may be modified in pathological conditions I will focus on the effects of the upregulation of the RE1-Silencing Transcription Factor (REST) observed in MS and related to alterations of neuronal excitability and axonal structure. This project will show how CF activity can modify its structure and PF plasticity rules, contributing to memory formation and disease.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology materials engineering fibers
- natural sciences chemical sciences inorganic chemistry alkali metals
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine neurology multiple sclerosis
- natural sciences physical sciences optics microscopy confocal microscopy
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-RI - RI – Reintegration panel
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
16163 Genova
Italy
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.