Physiology and Pathophysiology of the cerebellum in mouse models

We are seeking a consortium to join. We study neuronal physiology and plasticity at different levels (structural and functional, at the synaptic level as well as looking at intrinsic excitability) using the cerebellum as a model area, to better understand the mechanisms used in this circuit to encode information and memory. We also investigate pathological alterations of the structure and function of this circuit in brain diseases such as multiple sclerosis, autism, cerebellar ataxias and other neuropathologies.

RESEARCH TOPICS

• neuronal plasticity (structural and functional, at the synaptic level as well as looking at intrinsic excitability),

• learning and memory

• physiology and pathophysiology of the cerebellum

• multiple sclerosis

• cerebellar ataxia

• autism

• neuropsychiatric disorders

MAIN EXPERIMENTAL METHODS

• patch-clamp electrophysiology in acute brain slices and primary neuronal cultures

• in vivo microinjections

• viral vectors for gene expression/silencing

• immunohistochemistry

• fluorescent/confocal microscopy and morphometric analysis

AVAILABLE MOUSE MODELS

• L7-CRE: expressing the CRE recombinase in a Purkinje cell-specific way

• SK2-cKO: conditional CRE-dependente knock-out for SK2 (calcium-gated potassium channel Kcnn2)(Grasselli et al., 2020 PloS Biol)

• L7-SK2: Purkinje cell-specific knock-out of SK2 (Grasselli et al., 2020 PloS Biol)

• Frm1-KO: constitutive knock-out for the gene responsible for the Fragile-X syndrome

• Experimental Autoimmune Encephalomyelitis (EAE): mouse model for multiple sclerosis induced by immunization with a MOG antigen

WEBPAGE: https://www.iit.it/it/web/guest/people-profile/-/people/giorgio-grasselli

RELEVANT PUBLICATIONS

1. Grasselli G, Boele HJ, Titley H, Bradford N, van Beers L, Jay L, Beekhof GC, Busch SE, De Zeeuw C, Schonewille M, Hansel C  (2020) -SK2 channels in cerebellar Purkinje cells contribute to excitability modulation in motor-learning-specific memory traces, PLoS Biol 18(1):e3000596, PMID: 31905212, DOI: 10.1371/journal.pbio.3000596

2. Grasselli G, He Q, Wan V, Adelman JP, Ohtsuki G, Hansel C (2016) - Activity-dependent plasticity of spike pauses in cerebellar Purkinje cells, Cell Rep 14(11):2546–2553, PMID: 26972012, DOI: 10.1016/j.celrep.2016.02.054

3. Grasselli G, Rossi S, Musella A, Gentile A, Loizzo S, Muzio L, Di Sanza C, Errico F, Musumeci G, Haji N, Fresegna D, Sepman H, De Chiara V, Furlan R, Martino G, Usiello A, Mandolesi G, Centonze D (2013) - Abnormal NMDA receptor function exacerbates experimental autoimmune encephalomyelitis, Br J Pharmacol 168(2):502-17, PMID: 22924679, DOI: 10.1111/j.1476-5381.2012.02178.x

4. Mandolesi G, Grasselli G, Musella A, Sepman H, Musumeci G, Gentile A, Haji N, Fresegna D, Bernardi G, Centonze D (2012) - GABAergic signaling and connectivity on Purkinje cells are impaired in experimental autoimmune encephalomyelitis, Neurobiol Dis 46(2):414-24 PMID: 22349452, DOI: 10.1016/j.nbd.2012.02.005

5. Grasselli G, Mandolesi G, Strata P and Cesare P (2011) – I_mpaired sprouting and axonal atrophy in cerebellar climbing fibres following in vivo silencing of GAP-43_, PLoS One 6(6): e20791, PMID: 21695168, DOI: 10.1371/journal.pone.0020791 
   

FULL UPDATED LIST OF PUBLICATIONS

• ORCID (0000-0002-2942-9615): https://orcid.org/0000-0002-2942-9615

• Scopus (35573436500): https://www.scopus.com/authid/detail.uri?authorId=35573436500