ESR 11 - Alessandra Romei

Hosted at IIT 

ESR2 Round

Born in Italy, I obtained a M.Sc. in Integrative Biology specialised Neuroscience at the University Pierre et Marie Curie in Paris, France. My main interest in Neuroscience is the investigation of the mechanisms underlying neurological disorders and their treatment. For my master's project, I studied the implication of cortical GABAergic circuits in the beneficial effects of Deep Brain Stimulation for Parkinson's disease.

My goal within the ECMED project is to develop a MEA-based neurointerface allowing high resolution monitoring of the genesis and spread of epileptic activity, as well as for testing anti-convulsive drugs.


Development of MEA-based in vitro and ex vivo models of epileptogenesis and seizures for primary drug screening

Background

Multielectrode arrays (MEA)-based neurointerfaces provide an invaluable research tool for high-throughput and high-content accessing neuronal activity in-vitro,MEA extracellular recordings are non-invasive, have a high signal-to-noise ratio and permit high resolution monitoring of changes in excitability and spread of excitation in animal models of epilepsy.

Objectives

  • Test integrin-active reagents on the electrical activity of primary neurons and cortico-hippocampal slices.
  • Elucidate the role of the novel PRRT2 protein the maintenance and stability of synaptic transmission in high-density neuronal networks and in acute brain slices.
  • Investigate in vitro and in vivo the impact of DEPDC5 deficiency.

Approach

For rapid initial evaluation of ECM-targeting treatments, we will use an advanced electrophysiological approach based both on conventional MEAs and on a 64x64 (4096) CMOS-MEA device. This latter provides extracellular recordings with high spatial and temporal resolution, giving access both to single cells and to large-scale networks activity. We will evaluate the effect of ECM-targeting compounds (e.g. c(RGDfv) peptide and cilengetide) on the electrical activity of primary hippocampal neurons (from healthy rodents) and cortico-hippocampal slices rendered epileptic by acute treatment with convulsive agents. If the tested drugs are not significantly effective, the most promising compounds developed and characterized by other ESRs will be screened.

A MEA-based experimental approach will also be used to characterize the activity of neuronal networks which chronically lack PRRT2, a transmembrane protein recently identified as causative gene for a wide spectrum of neurological diseases sharing epileptic and paroxysmal features. PRRT2 most likely works as a synaptic adhesion molecule by.interacting with proteins of the ECM and/or with extracellular domains of synaptic proteins. We will record the activity of KO cortical and hippocampal networks under basal conditions and under acute treatment with bicuculline (to verify whether an imbalance between excitatory and inhibitory transmission occurs in this networks) and determine their responsiveness to external focal stimuli. Furthermore, because preliminary data revealed a strong expression of PRRT2 in the granule layer of the cerebellum, synaptic transmission in acute cerebellar slices from KO animals will be studies with high-resolution MEAs.

Loss-of-function mutations in DEPDC5 are the most common cause of familial focal epilepsies. DEPDC5 encodes a repressor of the mTORC1 cascade, which is a critical integrator of synaptic activity and extracellular signals that in turn affects cellular processes such as morphogenesis, protein and lipid synthesis, autophagy, actin dynamics. Patch-clamp recordings on primary autaptic neurons from homozygous and heterozygous DEPDC5 KO animals will be performed to investigate basal synaptic transmission, intrinsic excitability as well as short- and long-term synaptic plasticity. We will also assess the development of spontaneous seizures in vivo, by performing telemetric EEG recordings on these animals.

Collaborations

With DZNE, we will collaborate in the exploitation of high resolution MEA. The experimental models of epileptogenesis in vivo will be developed in collaboration with UCL and UEF (traumatic brain injury). 

ESR2

Born in Italy, I obtained a M.Sc. in Integrative Biology specialised Neuroscience at the University Pierre et Marie Curie in Paris, France. My main interest in Neuroscience is the investigation of the mechanisms underlying neurological disorders and their treatment. For my master's project, I studied the implication of cortical GABAergic circuits in the beneficial effects of Deep Brain Stimulation for Parkinson's disease.

My goal within the ECMED project is to develop a MEA-based neurointerface allowing high resolution monitoring of the genesis and spread of epileptic activity, as well as for testing anti-convulsive drugs.

Current Activity

Alessandra is working in the same laboratory at IIT, completing her thesis work in the 4th year of the PhD.

Page last modified on 21 may 19 11:27