Human brain contains about 80 billion neurons and an equal amount of astrocytes, the most abundant glial cell type (red and green cells in the panels). It has long been known that astrocytes play a crucial role for brain tissue homeosthasis. Notably, studies from the last two decades revealed that astrocytes also actively and finely modulate synaptic transmission and information processing, once considered exclusively neuronal functions. Indeed astrocytes, by releasing gliotransmitters and neurotrophins, modulate synaptic activity, cognitive functions and behaviour. In line with this, astrocytes and other glial cells like microglia have emerged as kew players and possible key targets in neurodegenerative diseases. Their function is highly complex, with both protective and detrimental effects on neuronal functions and survival. Advances in molecular biology tools and microscopy techniques on live tissue make now possible to study neuron-glia interactions with unprecedented detail. Our goal is to clarify these cellular and molecular mechanisms in order to unveil new therapeutic targets for brain disease. In particular we study Alzheimer’s disease, epilepsy and neuroinflammation with main focus on GABAergic and cholinergic systems, neurosteroids, neurotrophins and cytokines
| People | *Gabriele Losi, Gian Michele Ratto |
| Keywords | Astrocytes, Neurons, synapses, synaptic plasticity, Alzheimer’s disease, epilepsy |
| Methods, techniques | Laser scanning microscopy (single or two photons excitation); electrophysiology (patch-clamp and local field potential); immunofluorescence |
| Granted projects | PI of Unit for the PRIN 2020 (2020AMLXHH) entilted “Interaction between cholinergic and glutamatergic transmission at tripartite synapse in the pathophysiology of Alzheimer’s Disease”, coordinator: Prof. Claudio Grassi; (2022-2024) |
| Collaborations | University of Modena e Reggio Emilia (Jonathan Mapelli; Michele Zoli; Rita Bardoni; Giulia Puja); CNR-IN Padova section and University of Padova (Giorgio Carmignoto; Matteo Caleo); University of Trento (Marco Canossa); Georgetown University (Stefano Vicini) |
| Publications | |
| Requie, LM, Gómez-Gonzalo, M, Speggiorin, M, Managò, F, Melone, M, Congiu, M, Chiavegato, A, Lia, A, Zonta, M, Losi G, Jorge Henriques, V, Pugliese, A, Pacinelli, G, Marsicano, G, Papaleo, F, Muntoni, AL, Conti, F, Carmignoto, G (in stampa). Astrocytes mediate long-lasting synaptic regulation of ventral tegmental area dopamine neurons. Nature Neurosci, 2022 | |
| Puja G, Losi G, Rovati L, Lanza M, Caselli G and Bardoni R. Modulation of NMDA receptor activity by CR4056, an imidazoline-2 receptor ligand with analgesic properties. Front. Pain Res, 2022 | |
| Goisis RC, Chiavegato A, Gomez-Gonzalo M, Marcon I, Requie LM, Scholze P, Carmignoto G, Losi G. GABA tonic currents and glial cells are altered during epileptogenesis in a mouse model of Dravet syndrome. Front Cell Neurosci. 2022 | |
| Mastrogiacomo R, Trigilio G, Devroye C, Dautan D, Ferretti V, Losi G, Caffino L, Orso G, Marotta R, Maltese F, Vitali E, Piras G, Forgiarini A, Pacinelli G, Lia A, Rothmond DA, Waddington JL, Drago F, Fumagalli F, Luca MA, Leggio GM, Carmignoto G, Weickert CS, Managò F, Papaleo F. Dysbindin-1A modulation of astrocytic dopamine and basal ganglia dependent behaviors relevant to schizophrenia. Mol Psychiatry. 2022 | |
| Puja G, Ravazzini F, Losi G, Bardoni R, Battisti UM, Citti C, Cannazza G.J Benzothiadiazines derivatives as novel allosteric modulators of kainic acid receptors. J Physiol Pharmacol. 2022 | |
| A Lia, V J Henriques, M Zonta, A Chiavegato, G Carmignoto, M Gómez-Gonzalo and G Losi. Calcium Signals in Astrocyte Microdomains, a Decade of Great Advances. Front. Cell. Neurosci. 2021 | |
| A Maset, L Galla, S Francia, O Cozzolino, P Capasso, RC Goisis, G Losi, A Lombardo, GM Ratto, Lodovichi C. Altered Cl- homeostasis hinders forebrain GABAergic interneuron migration in a mouse model of intellectual disability. PNAS. 2021 | |
| L Mariotti, G Losi, A Lia, M Melone, A Chiavegato, M Gómez-Gonzalo, M Sessolo, S Bovetti, A Forli, M Zonta, LM Requie, I Marcon, A Pugliese, C Viollet, B Bettler, T Fellin, F Conti, G Carmignoto Interneuron-specific signaling evokes distinctive somatostatin-mediated responses in adult cortical astrocytes. Nature Communications. 2018 | |
| L Librizzi, G Losi, I Marcon, M Sessolo, P Scalmani, G Carmignoto, M de Curtis Interneuronal Network Activity at the Onset of Seizure-Like Events in Entorhinal Cortex Slices J Neurosci 2017 | |
| G Losi, L Mariotti, M Sessolo, G Carmignoto New Tools to Study Astrocyte Ca2+ Signal Dynamics in Brain Networks In Vivo. Front Cell Neurosci 2017 | |
| L Mariotti, G Losi, M Sessolo, I Marcon, G Carmignoto The inhibitory neurotransmitter GABA evokes long-lasting Ca2+ oscillations in cortical astrocytes. Glia 2016 | |
| M Sessolo, I Marcon, S Bovetti, G Losi, M Cammarota, GM Ratto, T Fellin, G Carmignoto Parvalbumin-positive inhibitory interneurons oppose propagation but favor generation of focal epileptiform activity. J Neurosci 2015 | |
| G Losi, L Mariotti, G Carmignoto GABAergic interneuron to astrocyte signalling: a neglected form of cell communication in the brain. Philos Trans R Soc Lond B Biol Sci 2014 | |
| M Cammarota, G Losi, A Chiavegato, M Zonta, G Carmignoto Fast spiking interneuron control of seizure propagation in a cortical slice model of focal epilepsy. J Physiol. 2013 | |
| G Losi, M Cammarota, G Carmignoto The role of astroglia in the epileptic brain Front Pharmacol 2012 | |
| M Gómez-Gonzalo, G Losi, A Chiavegato, M Zonta, M Cammarota, M Brondi, F Vetri, L Uva, T Pozzan, M de Curtis, GM Ratto, G Carmignoto An excitatory loop with astrocytes contributes to drive neurons to seizure threshold PLoS Biol 2010 | |
| G Losi, M Cammarota, A Chiavegato, M Gomez-Gonzalo, G Carmignoto A new experimental model of focal seizures in the entorhinal cortex Epilepsia 2010 | |
| G Losi, G Puia, G Garzon, MC de Vuono, M Baraldi Apigenin modulates GABAergic and glutamatergic transmission in cultured cortical neurons Eur J Pharmacol 2004 | |
| G Losi, K Prybylowski, Z Fu, J Luo, RJ Wenthold, S Vicini PSD-95 regulates NMDA receptors in developing cerebellar granule neurons. J Physiol 2003 | |
| G Losi, K Prybylowski, Z Fu, JH Luo, S Vicini Evidence of silent synapses in cerebellar granule cells J Neurophysiol 2002 |