Stefano Taverna RicercatoreMedicina
GABAergic interneurons play critical roles in the central nervous system, providing the greatest source of synaptic inhibition and regulating vital aspects of neuronal network dynamics.
A detailed knowledge of the large diversity and specific functions of interneurons is essential to understand the pathogenic mechanisms of several neurological disorders such as epilepsy, Parkinson’s disease, schizophrenia, and many others.
The ability to assess the involvement of different neuronal subpopulations in brain functions has represented one of the greatest challenges in neurobiology, but new research methods introduced in recent years―such as optogenetics and in vivo imaging techniques―are opening important novel routes of investigation
Our studies focus on the role of different types of GABAergic interneurons in animal models of neurological diseases. We are particularly interested in malfunctioning of basal ganglia synaptic microcircuits, mechanisms of initiation of epileptic tonic-clonic seizures, and synaptic defects involved in neuroinflammation and multiple sclerosis.
By using optogenetic tools combined with electrophysiological methods such as patch-clamp and local field recordings, we investigate how optical stimulation of specific interneuronal subtypes affects the electrical activity of principal neurons in basal ganglia and cerebral cortex. We also study the electrophysiological properties of neurons differentiated from induced pluripotent stem cells (iPS) obtained from human patients affected by multiple sclerosis and neurodegeneration with brain iron accumulation (NBIA).
2017-2019 Telethon GGP16234
Implementation of human neuronal cultures and mouse models of Pantothenate kinase 2 deficiency to investigate pathogenic mechanisms of iron-related neurodegeneration and evaluate Coenzyme A therapeutic efficacy.
2016-2018 Fondazione Italiana Sclerosi Multipla (F.I.S.M.) 2015/R/24
Homeostatic presynaptic mechanisms during chronic treatment of neurons with pro-inflammatory cytokines and in experimental autoimmune encephalitis.
2004: Ph.D. in Neuroscience, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands.
1995: M.S. in Biology, Department of Physiology and Biochemistry, University of Milan, Italy.
January 2015-present: Researcher, Neuroimmunology Unit, Division of Neuroscience, San Raffaele Hospital, Milan, Italy.
2009-14: Researcher, Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genoa, Italy.
2004-08: Postdoctoral fellow, Feinberg School of Medicine, Department of Physiology, Northwestern University, Chicago, IL, USA.
1999-2003: PhD student, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands.
1996-99: Research fellow, Department of Neurophysiology, C. Besta Neurological Institute, Milan, Italy.
1995-96: Research fellow, Laboratory of Antitumoral Pharmacology, M. Negri Institute of Pharmacological Research, Milan, Italy.
1995: Post-graduate training internship, Institute of Human Physiology, University of Milan, Italy.
1992-93: Pre-graduate training internship, Department of Physiology and Biochemistry, University of Milan, Italy.
Yekhlef L, Breschi GL, and Taverna S (2017). Optogenetic activation of VGLUT2-expressing excitatory neurons blocks epileptic seizure-like activity in the mouse entorhinal cortex. Scientific Reports 7: 43230. doi: 10.1038/srep43230.
Morè L, Künnecke B, Yekhlef L, Bruns A, Marte A, Fedele E, Bianchi V, Taverna S, Gatti S, D'Adamo P. (2017). Altered fronto-striatal functions in the Gdi1-null mouse model of X-linked Intellectual Disability. Neuroscience 344: 346-359. doi: 10.1016/j.neuroscience.2016.12.043.
Rubio A, Luoni M, Giannelli SG, Radice I, Iannielli A, Cancellieri C, Di Berardino C, Regalia G, Lazzari G, Menegon A, Taverna S, Broccoli V (2016). Rapid and efficient CRISPR/Cas9 gene inactivation in human neurons during human pluripotent stem cell differentiation and direct reprogramming. Scientific Reports 6: 37540. doi: 10.1038/srep37540.
Orellana DI, Santambrogio P, Rubio A, Yekhlef L, Cancellieri C, Dusi S, Giannelli SG, Venco P, Mazzara PG, Cozzi A, Ferrari M, Garavaglia B, Taverna S, Tiranti V, Broccoli V, Levi S (2016) Coenzyme A corrects pathological defects in human neurons of PANK2-associated neurodegeneration. EMBO Mol Med, pii: e201606391. doi: 10.15252/emmm.201606391.
Colasante G, Lignani G, Rubio A, Medrihan L, Yekhlef L, Sessa A, Massimino L, Giannelli SG, Sacchetti S, Caiazzo M, Leo D, Alexopoulou D, Dell’Anno MT, Ciabatti E, Orlando M, Studer M, Dahl MA, Gainetdinov R, Taverna S, Benfenati F, Broccoli V (2015) Rapid conversion of fibroblasts into functional forebrain GABAergic interneurons by direct genetic reprogramming. Cell Stem Cell, S1934-5909(15)00409-9. doi: 10.1016/j.stem.2015.09.002.
Broccoli V, Rubio A, Taverna S, Yekhlef L (2015) Overcoming the hurdles for a reproducible generation of human functionally mature reprogrammed neurons. Exp Biol Med, 240:787-794, doi: 10.1177/1535370215577585.
Yekhlef L, Breschi GL, Lagostena L, Russo G, and Taverna S (2014) Selective activation of parvalbumin- or somatostatin-expressing interneurons triggers epileptic seizure-like activity in the mouse medial entorhinal cortex. J Neurophysiol, 113: 1616-1630, doi:10.1152/jn.00841.2014.
Uva L, Breschi GL, Taverna S, and De Curtis M (2015) Synchronous inhibitory potentials precede seizure-like events in acute models of focal limbic seizures. J Neurosci 35: 3048-3055, doi: 10.1523/JNEUROSCI.3692-14.2015.
De Ceglia R, Chaabane L, Biffi E, Bergamaschi A, Ferrigno G, Amadio S, Del Carro U, Mazzocchi N, Comi G, Bianchi V, Taverna S, D’Adamo P, Martino GV, Menegon A, Muzio L (2014). Down-sizing of neuronal network activity and density of presynaptic terminals by pathological acidosis are efficiently prevented by Diminazene Aceturate, Brain Behav Imm, 45: 263-276, doi: 10.1016/j.bbi.2014.12.003.
Russo G and Taverna S (2014) Investigation of synaptic microcircuits using patch-clamp paired recordings in acute brain slices. In: Patch Clamp Methods and Protocols (M. Martina and S. Taverna, eds.), Springer, New York, pp. 183-193. doi: 10.1007/978-1-4939-1096-0_11.
Dell'Anno MT, Caiazzo M, Leo D, Dvoretskova E, Medrihan L, Colasante G, Giannelli S, Theka I, Russo G, Mus L, Pezzoli G, Gainetdinov RR, Benfenati F, Taverna S, Dityatev A, Broccoli V (2014). Remote control of induced dopaminergic neurons in parkinsonian rats. J Clin Invest 124: 3215-3229. doi: 10.1172/JCI74664.
Russo G, Nieus T, Maggi S, and Taverna S (2013). Dynamics of Action Potential Firing in Electrically Connected Striatal Fast-Spiking Interneurons. Front Cell Neurosci 7: 209, doi: 10.3389/fncel.2013.00209.
Bonifazi P, Difato F, Massobrio P, Breschi GL, Pasquale V, Levi T, Goldin M, Bornat Y, Tedesco M, Bisio M, Kanner S, Galron R, Tessadori J, Taverna S, Chiappalone M. (2013). In vitro large-scale experimental and theoretical studies for the realization of bi-directional brain-prostheses. Front Neural Circuits 7, doi:10.3389/fncir.2013.00040.
Caiazzo M, Dell'Anno MT, Dvoretskova E, Lazarevic D, Taverna S, Leo D, Sotnikova T, Menegon A, Roncaglia P, Colciago P, Russo G, Carninci P, Pezzoli G, Gainetdinov R, Gustincich S, Dityatev A, and Broccoli V (2011). Direct Generation of Functional Dopaminergic Neurons from Mouse and Human Fibroblasts. Nature 476: 224-227. doi:10.1038/nature10284.
Taverna S, Ilijic E, and Surmeier DJ (2008). Recurrent collateral connections of striatal medium spiny neurons are disrupted in models of Parkinson’s disease. J Neurosci 28:5504-5512.
Taverna S and Pennartz CM (2008). Intrinsic synaptic connectivity of the nucleus accumbens: lateral inhibition, functions of fast-spiking interneurons, and neuromodulation. In: The Nucleus Accumbens: Neurotransmitters and Related Behaviors, (H.N. David, ed.), Research Signpost, Kerala, India, pp. 63-80.
Taverna S, Canciani B, and Pennartz CM (2007). Membrane properties and synaptic connectivity of fast-spiking interneurons in rat ventral striatum. Brain Res 1152: 49-56.
Taverna S, Tkatch T, Metz AE, and Martina M (2005). Differential expression of TASK channels between horizontal interneurons and pyramidal cells of rat hippocampus. J Neurosci 25: 9162-9170.
Taverna S, Canciani B, and Pennartz CM (2005). Dopamine D1-receptors modulate lateral inhibition between principal cells of the nucleus accumbens. J Neurophysiol 93: 1816-1819.
Taverna S, van Dongen YC, Groenewegen HJ, and Pennartz CM (2004). Direct physiological evidence for synaptic connectivity between medium-sized spiny neurons in rat nucleus accumbens in situ. J Neurophysiol 91: 1111-1121.
Taverna S and Pennartz CM (2003). Postsynaptic modulation of AMPA- and NMDA-receptor currents by Group III metabotropic glutamate receptors in rat nucleus accumbens. Brain Res 976: 60-68.
Frassoni C, Spreafico R, Franceschetti S, Aurisano N, Bernasconi P, Garbelli R, Antozzi C., Taverna S, Granata T, and Mantegazza R (2001) Labeling of rat neurons by anti-GluR3 IgG from patients with Rasmussen encephalitis. Neurology 57: 324-327.
Franceschetti S, Taverna S, Sancini G, Panzica F, Lombardi R, and Avanzini G (2000). Protein kinase C–dependent modulation of Na+ currents increases the excitability of rat neocortical pyramidal neurons. J Physiol 528: 291-304.
Taverna S, Sancini G, Mantegazza M, Franceschetti S, and Avanzini G (1999). Inhibition of transient and persistent Na+ currents by the new anticonvulsant Topiramate. J Pharm Exp Ther. 288: 960-968.
Erba E, Bergamaschi D, Ronzoni S, Faretta M, Taverna S, Bonfanti M, Catapano CV, Faircloth G, Jimeno J, D'Incalci M Mode of action at thiocoraline, a natural marine compound with anti-tumor activity (1999). Br J Cancer 80: 971-980.
Taverna S, Mantegazza M, Franceschetti S, and Avanzini G (1998). Valproate selectively reduces the persistent fraction of Na+ current in neocortical neurons. Epilepsy Res. 32: 304-308.
Bergamaschi D, Ronzoni S, Taverna S, Faretta M, De Feudis P, Faircloth G, Jimeno J, Erba E, D'Incalci M (1999). Cell cycle perturbations and apoptosis induced by isohomohalichondrin B (IHB), a natural marine compound. Br J Cancer 79: 267-277.
Faretta M, Bergamaschi D, Taverna S, Ronzoni S, Pantarotto M, Mascellani E, Cappella P, and Erba E (1998). Characterization of cyclin B1 expression in human cancer cell lines by a new three-parameter BrdUrd/cyclin B1/DNA analysis. Cytometry, 31: 53-59.
Bonfanti M, Taverna S, Salmona M, D’Incalci M, and Broggini M (1997). p21WAF1-Derived Peptides Linked to an Internalization Peptides Inhibit Human Cancer Cell Gowth. Cancer Res 57: 1442-1446.
Bergamaschi D, Faretta M, Ronzoni, S, Taverna, S, De Feudis, P, Bonfanti, M, Guidi, G, Faircloth, M, Jimeno, J, D'Incalci, M, Erba, E (1997). Flow cytometric analysis of cell cycle phase perturbations induced by Thiocoraline, a new marine-derived anticancer compound. Eur J Histochem 41, Suppl.2: 63-64.
Songia S, Mortellaro A, Taverna S, Fornasiero C, Scheiber E A, Erba E, Colotta F, Mantovani A, Isetta AM, and Golay J (1997). Characterization of the immunosuppressive drug undecylprodigiosin in human lymphocytes: retinoblastoma protein, Cdk2 and Cdk4 as molecular targets. J Immunol 158: 3987-3995.
Formenti A, Arrigoni E, Martina M, Taverna S, Avanzini G, and Mancia M. (1995) Calcium influx in rat thalamic relay neurons through voltage-dependent calcium channels is inhibited by enkephalin. Neurosci Lett 201: 21-24.
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