Synaptic neurophysiology (Prof. Cingolani)

Research Strand:

Associate Professor in Physiology (BIO/09)

Phone: +39 040 5588728
Email: lcingolani@units.it
Skype: la.cingolani
Twitter: @CingolaniLab

Biosketch

After graduating in Molecular Biology at the University of Pisa (Italy), I obtained a Ph.D. fellowship to work at the Max-Planck Institute for Experimental Medicine, Göttingen (Germany). Here, I specialized in electrophysiology under the guidance of Prof. Walter Stühmer and Prof. Paola Pedarzani, receiving a Ph.D. in Neurobiology from the Humboldt University of Berlin in 2002.

Driven by my interests in synaptic physiology, I joined Dr. Yukiko Goda’s research group at the MRC Laboratory for Molecular and Cell Biology - University College London (UCL, UK) as a postdoctoral fellow and research associate. In this innovative and integrative research environment, I identified a previously unsuspected requirement for integrin adhesion complexes in homeostatic synaptic plasticity. These findings highlighted the importance of biomechanical properties of the brain in health and disease.

In 2012, I established my laboratory at the Italian Institute of Technology (IIT; Genoa). With the aim of elucidating the molecular bases of functional connectivity in the brain, we demonstrated that alternative splicing of Ca2+ channels is crucial in shaping synaptic strength. Furthermore, we implemented optogenetic and genome editing approaches to translate our latest findings into rational therapeutic strategies for autism, epilepsy and ataxia.

In 2019, I joined the University of Trieste as Associate Professor of Physiology, where I direct the Laboratory of Synaptic Neurophysiology.

Info

Research

Our research aims to identify the general principles governing assembly and remodeling of synaptic connections in the mammalian brain. Understanding the molecular mechanisms that control development and function of neural networks is essential for treating neurological and psychiatric disorders.

Quite possibly the most complex organ in the body, the brain determines our behaviors, thoughts and identity. Activity-dependent changes in brain structure and function enables us to form new memories and learn new skills. Alterations in brain connectivity and excitability can however lead to disabling brain disorders, such as epilepsy, autism, depression and ataxia.

Brain function: Focus on cell adhesion molecules and calcium channels

Brain function critically depends on how neurons interact and communicate with each other at synapses. Our goal is to identify the molecular mechanisms governing formation, specialization and remodeling of synaptic connections in the mammalian cortex.

Synapses can be viewed as both learning and memory storage devices. On the one hand, they are highly ‘plastic’, changing how they transmit information in response to changes in brain activity. On the other hand, they can be highly ‘tenacious’, with many synapses retaining their structural and functional properties over many years. Our overarching interest is in how synapses achieve the right balance between plasticity and tenacity, and how disrupting this equilibrium contributes to neurological disorders.

In particular, we investigate how (i) synaptic cell adhesion molecules determine synapse specificity and (ii) how alternative splicing of calcium channels contributes to synapse diversity. We approach these questions from molecular, network and behavioral perspectives, to gain a comprehensive understanding of brain function.

We are committed to using our discoveries to develop effective treatments for brain disorders to improve patients’ health and quality of life.

Current projects

Synaptic magneto-genetics

www.synmech.eu

Our team is dedicated to developing an innovative technology called synaptic magnetogenetics that will allow for the precise control of neural circuit connectivity in the brain. We believe that this technology has the potential to revolutionize the way we treat high-prevalence treatment-resistant brain disorders.

Magnetogenetics is an emerging field of health science that merges the strengths of optogenetics and magneto-mechanical stimulations. Like optogenetics, magnetogenetics employs actuators to target specific neural circuits, while exploiting magnetic fields, rather than light, to achieve non-invasive brain stimulation.

Here, we implement an innovative solution for magnetogenetics based on biocompatible magnetic nanoparticles and bioengineered synaptic mechanosensors that work together to regulate brain connectivity in response to focused magnetic fields, delivered via high-permeability transcranial magnetic stimulators. We assess the capacity of the synaptic mechanogenetic toolkit to normalize network activity in mouse models of stroke, epilepsy, autism and depression.

Collaborators: University of Verona, Forschungszentrum Julich (Germany), Brain Science tools (The Netherlands), CNR (Milan), Deutsches Zentrum für Neurodegenerative Erkrankungen (Germany), Universitair Medisch Centrum Utrecht (The Netherlands) and Ca’ Granda Hospital (Milan).

Project supported by the European Research Council (SynMech; Horizon-EIC-2022-Pathfinderopen-01-01; grant ID: 101099579), the Cariplo Foundation (DIGAP; grant ID: 2019-3438) and the Ministry of Health (DRACULA; Finalized research; grant ID: GR-2021-12375009).

CRISPR/Cas9-dependent regulation of alternative splicing as an all-purpose genetic therapy for episodic ataxia and absence epilepsy

We have developed a CRISPR/Cas9-mediated genome editing strategy to control alternative splicing as an all-purpose genetic therapy for neurological disorders caused by loss-of-function mutations in the synaptic calcium channel Ca_V2.1. These disorders include episodic ataxia type 2 and absence epilepsy.

Optogenetic experiments show that our approach is highly effective in rescuing network excitability defects in human iPSC-induced neurons carrying Ca_V2.1 mutations, as well as electrophysiological and behavioral abnormalities in Ca_V2.1-deficient mice.

Collaborators: Pediatric Hospital Gaslini (Genoa).

Project supported by the Telethon foundation (grant ID: GGP19181), the Telethon and Cariplo foundations (grant ID: GJC22053) and the University of Trieste.

People

Postdocs

Fanny Jaudon
fjaudon@units.it

PhD students

Riccardo Ruggeri
riccardo.ruggeri@phd.units.it

Jessica Muià
jessica.muia@phd.units.it

Sara Riccardi
sara.riccardi@phd.units.it

Asja Ragnini
asja.ragnini@phd.units.it

Project manager

Lucia Celora
lucia.celora@phd.units.it

Studenti

Kankana Dutta
kankana.dutta@studenti.units.it

Publications

Full list of the publications of the Principal Investigator

Scopus
ORCID
Google scholar

Selected papers

Moretto, E., Longatti, A., Miozzo, F., Bonnet, C., Coussen, F., Jaudon, F., Cingolani, L.A., and Passafaro, M. (2023). The tetraspanin TSPAN5 regulates AMPARs exocytosis by interacting with the AP-4 complex. Elife, in press. Full text
Jaudon, F., Thalhammer, A., Zentilin, L., and Cingolani, L.A. (2022). CRISPR-mediated activation of autism gene Itgb3 restores cortical network excitability via mGluR5 signaling. Mol Ther Nucleic Acids 29, 462-480. Full text
Ferrante, D., Sterlini, B., Prestigio, C., Marte, A., Corradi, A., Onofri, F., Tortarolo, G., Vicidomini, G., Petretto, A., Muia, J., Thalhammer, A., Valente, P., Cingolani, L.A., Benfenati, F., and Baldelli, P. (2021). PRRT2 modulates presynaptic Ca(2+) influx by interacting with P/Q-type channels. Cell Rep 35, 109248. Full text
Thalhammer, A., Contestabile, A., Ermolyuk, Y.S., Ng, T., Volynski, K.E., Soong, T.W., Goda, Y., and Cingolani, L.A. (2017). Alternative Splicing of P/Q-Type Ca²⁺ Channels Shapes Presynaptic Plasticity. Cell Rep 20, 333-343. Full text
Bassani, S., Cingolani, L.A., Valnegri, P., Folci A., Zapata, J., Gianfelice, A., Sala, C., Goda, Y., and Passafaro., M. (2012) TSPAN7, a protein involved in X-linked intellectual disability, promotes development of excitatory synapses and regulates AMPAR trafficking through interaction with PICK1. Neuron 73, 1143-1158. Full text
Pozo, K., Cingolani, L.A., Bassani, S., Laurent, F., Passafaro, M. and Goda, Y. (2012) β3 integrin interacts directly with GluA2 AMPA receptor subunit and regulates AMPA receptor expression in hippocampal neurons. Proc Natl Acad Sci USA 109, 1323-1328. Full text
Thalhammer, A., Edgington, R. J., Cingolani, L.A., Schoepfer, R., and Jackman, R. B. (2010). The use of nanodiamond monolayer coatings to promote the formation of functional neuronal networks. Biomaterials 31, 2097-2104. Full text
Cingolani, L.A., Thalhammer, A., Yu, L. M., Catalano, M., Ramos, T., Colicos, M. A., and Goda, Y. (2008). Activity-Dependent Regulation of Synaptic AMPA Receptor Composition and Abundance by β3 Integrins. Neuron 58, 749-762. Full text
Okuda, T., Yu, L. M., Cingolani, L.A., Kemler, R., and Goda, Y. (2007). β-Catenin regulates excitatory postsynaptic strength at hippocampal synapses. Proc Natl Acad Sci USA 104, 13479-13484. Full text
Cingolani, L.A., Gymnopoulos, M., Boccaccio, A., Stocker, M., and Pedarzani, P. (2002). Developmental regulation of small-conductance Ca²⁺-activated K⁺ channel expression and function in rat Purkinje neurons. J Neurosci 22, 4456-4467. Full text

Notices

We are seeking motivated and talented students and postdocs to join our team in the framework of the European Research Council project SynMech - A synaptic mechanogenetic technology to repair brain connectivity (www.synmech.eu; Horizon-EIC-2022-Pathfinderopen-01-01; grant ID: 101099579). Our collaborative team, consisting of the University of Trieste and six other European research institutes (University of Verona, Forschungszentrum Julich (Germany), Brain Science tools (The Netherlands), CNR (Milan), Deutsches Zentrum für Neurodegenerative Erkrankungen (Germany) and Universitair Medisch Centrum Utrecht (The Netherlands), offers opportunities for student exchanges between institutes. For further information about the SynMech project or to inquire about open positions, please contact lcingolani@units.it

Last update: 09-19-2025 - 23:30

Hide/Show