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Multilevel characterization of CNS activity alterations in disease models

 

 

 

Most of the central nervous system disorders involve alterations in neuronal excitability, excitatory/inhibitory balance, short- and long-term plasticity, short- and long-range functional connectivity, with behavioral consequences. It is therefore of pivotal importance to investigate these diseases using a multilevel approach. In the lab, research lines are active to characterize the alterations present in several neurodevelopmental and neurological disorders, such as autism, dystonia, ataxia, paroxysmal dyskinesia, migraine, schizophrenia, PCDH19-related developmental and epileptic encephalopathy-9. The research plan often includes the combination of whole-cell patch-clamp, high-density multielectrode arrays, two-photon calcium imaging, in vivo electrophysiological and imaging recordings, and behavioral testing to obtain a comprehensive multilevel characterization of the disease and to reconstruct how the alterations in single neurons and networks determine the behavioral pathological phenotype.

 

A PhD student joining this general topic will have the opportunity to learn how to implement a wide research plan to investigate a CNS disorder, working in a collaborative environment and in close contact with the other researchers involved. For the description of the techniques used, see the corresponding sections.

 

References

Soda T, Mapelli L, Locatelli F, Botta L, Goldfarb M, Prestori F, D’Angelo E. Hyperexcitability and Hyperplasticity Disrupt Cerebellar Signal Transfer in the IB2 KO Mouse Model of Autism. J Neurosci. 2019 Mar 27;39(13):2383-2397. doi: 10.1523/JNEUROSCI.1985-18.2019. Epub 2019 Jan 29. Erratum in: J Neurosci. 2019 Aug 28;39(35):7029. doi: 10.1523/JNEUROSCI.1459-19.2019. PMID: 30696733; PMCID: PMC6435825.

Faris P, Pischedda D, Palesi F, D’Angelo E. New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment. Front Cell Neurosci. 2024 May 10;18:1386583. doi: 10.3389/fncel.2024.1386583. PMID: 38799988; PMCID: PMC11116653.

Mapelli L, Soda T, D’Angelo E, Prestori F. The Cerebellar Involvement in Autism Spectrum Disorders: From the Social Brain to Mouse Models. Int J Mol Sci. 2022 Mar 31;23(7):3894. doi: 10.3390/ijms23073894. PMID: 35409253; PMCID: PMC8998980.