ESR 10 - Eduardo Morais

Hosted at IIT

ESR3 round

I have a Bachelor's degree in Biology and a Master's degree in Cellular and Molecular Biology with specialisation in Neurobiology, both from the University of Coimbra, Portugal. The study of synaptic plasticity (the regulation of the communication between neurons) is my main scientific interest. For my Master's project, I studied the regulation of hnRNP K levels in dendrites, a protein important for local protein synthesis.

With ECMED, I aim at studying the synaptic functions of αv integrin and how it could be related to propensity for epilepsy.



Elucidation of causality between αV integrin deficiency and epilepsy



Background

Deficiencies in αV integrins lead to axonal degeneration, ataxia and epileptic seizures. We hypothesize that an αV integrin-dependent reduction in axonal projections alters the ratio of excitation to inhibition and/or triggers homeostatic hyper-excitability, thus leading to spontaneous seizures.  

Objectives

  • To characterize the cellular and molecular defects of αV conditional KO (cKO) mice
  • to assess whether morphological and/or physiological defects can be reversed by viral approaches
  • to verify the role of the above studied mechanisms for epileptogenesis in vivo

Approach

We will use a cKO mouse where αV integrin is selectively ablated in excitatory neurons of the forebrain. Confocal imaging will be used to determine alterations in the spatial pattern of excitatory axons before (6 weeks) and after (3 months) the appearance of epileptic seizures. Patch-clamp recordings from pyramidal and inhibitory neurons of the hippocampus will be performed at 6 weeks and 3 months to investigate basal synaptic transmission, short- and long-term forms of synaptic plasticity in response to optogenetic stimulations. Additionally, the intrinsic excitability of hippocampal neurons will be evaluated. Electrophysiological data will be complemented by two photon Ca2+ imaging in presynaptic boutons expressing the genetically encoded and synaptically localized Ca2+ indicator Synaptophysin-GCaMP6s (SyGCaMP6s), to investigate presynaptic Ca2+ homeostasis. To assess whether the identified defects are reversible, integrin αV will be virally reintroduced in αV integrin cKO mice before and after the onset of epileptic seizures. To verify the role of the above studied mechanisms for epileptogenesis in vivo, we will monitor the development of spontaneous seizures in integrin αV cKO mice, and test whether virally reintroducing αV integrin prevents/reduces the development of epileptic seizures.  

Collaborations

With DZNE, we will investigate presynaptic calcium homeostasis by two photon Ca2+ imaging. Epileptogenesis in vivo will be studied in collaboration with UCL and UEF.

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