Matteo Caleo is a Full Professor of Physiology at Dept. of Biomedical Sciences in Padua and Research Associate at CNR Neuroscience Institute in Pisa. He graduated cum laude in Biological Sciences at the Scuola Normale Superiore in Pisa. He obtained his PhD in Neurobiology working with Lamberto Maffei on the role of neurotrophins in activity-dependent plasticity of the visual cortex. He has spent several years as a Research Scientist and then Director of Research at the CNR Neuroscience Institute in Pisa, where he studies plasticity of neuronal connections in pathological brain conditions.
Since October 2018, he is Professor of Physiology at the Dept of Biomedical Sciences, where he is settting up his lab devoted to plasticity and recovery in stroke and brain tumors.
EDUCATION
1994 Degree in Biological Sciences, University of Pisa
1994 Diploma in Biological Sciences, Scuola Normale Superiore, Pisa
1998 Ph.D. in Neurobiology, Scuola Normale Superiore
1998 Fellow, Levi-Montalcini Foundation, Rome, Italy
1999 Postdoctoral Fellow, Scuola Normale Superiore, Pisa, Italy
2000 Visiting fellow, Yale University
RESEARCH INTERESTS
Neuronal plasticity in brain pathological conditions
Combining gamma neuromodulation and robotic rehabilitation after a stroke restores parvalbumin interneuron dynamics and improves motor recovery in mice Livia Vignozzi, Francesca Macchi, Elena Montagni, Maria Pasquini, Alessandra Martello, et al. Plos Biology, 2025 Stroke is a leading cause of long-term disability, frequently associated with persistent motor deficits. Gamma band oscillations, generated by synchronous discharge of parvalbumin-positive interneurons (PV-INs), are critically affected after stroke in humans and animals. Both gamma band and PV-INs play a key role in motor function, thus representing a promising target for poststroke neurorehabilitation. Noninvasive neuromodulatory approaches are considered a safe intervention and can be used for this purpose. Here, we present a novel, clinically relevant, noninvasive, and well-tolerated sub-acute treatment combining robotic rehabilitation with advanced neuromodulation techniques, validated in a mouse model of ischemic injury. During the sub-acute poststroke phase, we scored profound deficits in motor-related gamma band activity in the perilesional cortex. These deficits were accompanied by reduced PV-IN firing rates and increased functional connectivity, both at the perilesional and at the whole-cortex levels. Therefore, we tested the therapeutic potential of coupling robotic rehabilitation with optogenetic PV-IN-driven gamma band stimulation in a subacute poststroke phase during motor training to reinforce the efficacy of the treatment. Frequency-specific movement-related gamma band stimulation, when combined with physical training, significantly improved forelimb motor function. More importantly, by pairing robotic rehabilitation with a clinical-like noninvasive 40 Hz transcranial Alternating Current Stimulation, we achieved similar motor improvements mediated by the effective restoring of movement-related gamma band power, improvement of PV-IN maladaptive network dynamics, and increased PV-IN connections in premotor cortex. Our research introduces a new understanding of the role of parvalbumin-interneurons in poststroke impairment and recovery. These results highlight the synergistic potential of combining perilesional gamma band stimulation with robotic rehabilitation as a promising and realistic therapeutic approach for stroke patients.
Molecular changes underlying decay of sensory responses and enhanced seizure propensity in peritumoral neurons Elena Tantillo, Marta Scalera, Elisa De Santis, Nicolò Meneghetti, Chiara Cerri, et al. Neuro Oncology, 2023 Background Glioblastoma growth impacts on the structure and physiology of peritumoral neuronal networks, altering the activity of pyramidal neurons which drives further tumor progression. It is therefore of paramount importance to identify glioma-induced changes in pyramidal neurons, since they represent a key therapeutic target. Methods We longitudinal monitored visual evoked potentials after the orthotopic implant of murine glioma cells into the mouse occipital cortex. With laser microdissection, we analyzed layer II-III pyramidal neurons molecular profile and with local field potentials recordings we evaluated the propensity to seizures in glioma-bearing animals with respect to control mice. Results We determine the time course of neuronal dysfunction of glioma-bearing mice and we identify a symptomatic stage, based on the decay of visual response. At that time point, we microdissect layer II-III pyramidal neurons and evaluate the expression of a panel of genes involved in synaptic transmission and neuronal excitability. Compared to the control group, peritumoral neurons show a decrease in the expression of the SNARE complex gene SNAP25 and the alpha1 subunit of the GABA-A receptor. No significant changes are detected in glutamatergic (ie, AMPA or NMDA receptor subunit) markers. Further reduction of GABA-A signaling by delivery of a benzodiazepine inverse agonist, DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) precipitates seizures in 2 mouse models of tumor-bearing mice. Conclusions These studies reveal novel molecular changes that occur in the principal cells of the tumor-adjacent zone. These modifications may be therapeutically targeted to ameliorate patients’ quality of life.
Fast-Spiking Interneurons of the Premotor Cortex Contribute to Initiation and Execution of Spontaneous Actions Nadia Giordano, Claudia Alia, Lorenzo Fruzzetti, Maria Pasquini, Giulia Palla, et al. Journal of Neuroscience, 2023 Planning and execution of voluntary movement depend on the contribution of distinct classes of neurons in primary motor and premotor areas. However, timing and pattern of activation of GABAergic cells during specific motor behaviors remain only partly understood. Here, we directly compared the response properties of putative pyramidal neurons (PNs) and GABAergic fast-spiking neurons (FSNs) during spontaneous licking and forelimb movements in male mice. Recordings centered on the face/mouth motor field of the anterolateral motor cortex (ALM) revealed that FSNs fire longer than PNs and earlier for licking, but not for forelimb movements. Computational analysis revealed that FSNs carry vastly more information than PNs about the onset of movement. While PNs differently modulate their discharge during distinct motor acts, most FSNs respond with a stereotyped increase in firing rate. Accordingly, the informational redundancy was greater among FSNs than PNs. Finally, optogenetic silencing of a subset of FSNs reduced spontaneous licking movement. These data suggest that a global rise of inhibition contributes to the initiation and execution of spontaneous motor actions.SIGNIFICANCE STATEMENTOur study contributes to clarifying the causal role of fast-spiking neurons (FSNs) in driving initiation and execution of specific, spontaneous movements. Within the face/mouth motor field of mice premotor cortex, FSNs fire before pyramidal neurons (PNs) with a specific activation pattern: they reach their peak of activity earlier than PNs during the initiation of licking, but not of forelimb, movements; duration of FSNs activity is also greater and exhibits less selectivity for the movement type, as compared with that of PNs. Accordingly, FSNs appear to carry more redundant information than PNs. Optogenetic silencing of FSNs reduced spontaneous licking movement, suggesting that FSNs contribute to the initiation and execution of specific spontaneous movements, possibly by sculpting response selectivity of nearby PNs.
Long-term beneficial impact of the randomised trial ‘Train the Brain’, a motor/cognitive intervention in mild cognitive impairment people: effects at the 14-month follow-up Alessandro Sale, Marianna Noale, Simona Cintoli, Gloria Tognoni, Chiara Braschi, et al. Age and Ageing, 2023 No treatment options are currently available to counteract cognitive deficits and/or delay progression towards dementia in older people with mild cognitive impairment (MCI). The ‘Train the Brain’ programme is a combined motor and cognitive intervention previously shown to markedly improve cognitive functions in MCI individuals compared to non-trained MCI controls, as assessed at the end of the 7-month intervention. Here, we extended the previous analyses to include the long-term effects of the intervention and performed a data disaggregation by gender, education and age of the enrolled participants. We report that the beneficial impact on cognitive functions was preserved at the 14-month follow-up, with greater effects in low-educated compared to high-educated individuals, and in women than in men.
Disruption of layer-specific visual processing in a model of focal neocortical epilepsy Alessandro Panarese, Matteo Vissani, Nicolò Meneghetti, Eleonora Vannini, Marina Cracchiolo, et al. Cerebral Cortex, 2023 The epileptic brain is the result of a sequence of events transforming normal neuronal populations into hyperexcitable networks supporting recurrent seizure generation. These modifications are known to induce fundamental alterations of circuit function and, ultimately, of behavior. However, how hyperexcitability affects information processing in cortical sensory circuits is not yet fully understood. Here, we investigated interlaminar alterations in sensory processing of the visual cortex in a mouse model of focal epilepsy. We found three main circuit dynamics alterations in epileptic mice: (i) a spreading of visual contrast-driven gamma modulation across layers, (ii) an increase in firing rate that is layer-unspecific for excitatory units and localized in infragranular layers for inhibitory neurons, and (iii) a strong and contrast-dependent locking of firing units to network activity. Altogether, our data show that epileptic circuits display a functional disruption of layer-specific organization of visual sensory processing, which could account for visual dysfunction observed in epileptic subjects. Understanding these mechanisms paves the way to circuital therapeutic interventions for epilepsy.
Facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanus Federico Fabris, Stefano Varani, Marika Tonellato, Ivica Matak, Petra Šoštarić, et al. Jci Insight, 2023 Cephalic tetanus (CT) is a severe form of tetanus that follows head wounds and the intoxication of cranial nerves by tetanus neurotoxin (TeNT). Hallmarks of CT are cerebral palsy, which anticipates the typical spastic paralysis of tetanus, and rapid evolution of cardiorespiratory deficit even without generalized tetanus. How TeNT causes this unexpected flaccid paralysis, and how the canonical spasticity then rapidly evolves into cardiorespiratory defects remain unresolved aspects of CT pathophysiology. Using electrophysiology and immunohistochemistry, we demonstrate that TeNT cleaves its substrate VAMP within facial neuromuscular junctions and causes a botulism-like paralysis overshadowing its canonical spasticity. Meanwhile, TeNT spreads among brainstem neuronal nuclei and, as shown by an assay to monitor the ventilation ability of CT mice, it harms essential functions like respiration. A partial axotomy of the facial nerve revealed a still-unknown ability of TeNT to undergo intra-brainstem diffusion, which allows the toxin to spread onto brainstem nuclei devoid of direct peripheral efferents. Other showing a mechanism possibly involved in the transition from local to generalized tetanus, these findings suggest that patients with idiopathic facial nerve palsy should be immediately considered for CT and treated with antisera to block the potential progression of a life-threatening form of tetanus.
Synaptic alterations in visual cortex reshape contrast-dependent gamma oscillations and inhibition-excitation ratio in a genetic mouse model of migraine Nicolò Meneghetti, Chiara Cerri, Eleonora Vannini, Elena Tantillo, Angelita Tottene, et al. Journal of Headache and Pain, 2022 Background Migraine affects a significant fraction of the world population, yet its etiology is not completely understood. In vitro results highlighted thalamocortical and intra-cortical glutamatergic synaptic gain-of-function associated with a monogenic form of migraine (familial-hemiplegic-migraine-type-1: FHM1). However, how these alterations reverberate on cortical activity remains unclear. As altered responsivity to visual stimuli and abnormal processing of visual sensory information are common hallmarks of migraine, herein we investigated the effects of FHM1-driven synaptic alterations in the visual cortex of awake mice. Methods We recorded extracellular field potentials from the primary visual cortex (V1) of head-fixed awake FHM1 knock-in (n = 12) and wild type (n = 12) mice in response to square-wave gratings with different visual contrasts. Additionally, we reproduced in silico the obtained experimental results with a novel spiking neurons network model of mouse V1, by implementing in the model both the synaptic alterations characterizing the FHM1 genetic mouse model adopted. Results FHM1 mice displayed similar amplitude but slower temporal evolution of visual evoked potentials. Visual contrast stimuli induced a lower increase of multi-unit activity in FHM1 mice, while the amount of information content about contrast level remained, however, similar to WT. Spectral analysis of the local field potentials revealed an increase in the β/low γ range of WT mice following the abrupt reversal of contrast gratings. Such frequency range transitioned to the high γ range in FHM1 mice. Despite this change in the encoding channel, these oscillations preserved the amount of information conveyed about visual contrast. The computational model showed how these network effects may arise from a combination of changes in thalamocortical and intra-cortical synaptic transmission, with the former inducing a lower cortical activity and the latter inducing the higher frequencies ɣ oscillations. Conclusions Contrast-driven ɣ modulation in V1 activity occurs at a much higher frequency in FHM1. This is likely to play a role in the altered processing of visual information. Computational studies suggest that this shift is specifically due to enhanced cortical excitatory transmission. Our network model can help to shed light on the relationship between cellular and network levels of migraine neural alterations. Graphical Abstract
Combining gamma neuromodulation and robotic rehabilitation after a stroke restores parvalbumin interneuron dynamics and improves motor recovery in mice L Vignozzi, F Macchi, E Montagni, M Pasquini, A Martello, A Minetti, ... Plos Biology 23 (10), e3002806 , 2025 2025 Citations: 2
Inhibitory circuit dysfunction as a potential contributor to cortical reorganization in Glioblastoma progression C Spalletti, M Scalera, E Mori, S Haddad, M Mainardi, D Cangi, V Pillai, ... Neurobiology of Disease 213, 106997 , 2025 2025 Citations: 3
Modulation of the spread of pathological tau in vitro and in vivo C Panzi UCL (University College London) , 2025 2025
P02. 18. A MOLECULAR CHANGES UNDERLYING DECAY OF SENSORY RESPONSES AND ENHANCED SEIZURE PROPENSITY IN PERITUMORAL NEURONS E De Santis, E Tantillo, M Scalera, N Meneghetti, C Cerri, M Menicagli, ... Neuro-Oncology 26 (Suppl 5), v39 , 2024 2024
P02. 22. A REARRANGEMENTS OF PERITUMORAL TISSUE THAT OCCUR ALONG WITH GLIOMA PROGRESSION E Mori, C Spalletti, M Scalera, S Haddad, D Cangi, V Pillai, E Parmigiani, ... Neuro-Oncology 26 (Suppl 5), v40 , 2024 2024
P02. 17. B MANIPULATING GABAERGIC MECHANISMS TO DELAY GLIOMA INVASION IN PERITUMORAL MICROENVIRONMENT M Scalera, E De Santis, AS Verduri, N Meneghetti, N Barsotti, E Novelli, ... Neuro-Oncology 26 (Suppl 5), v38 , 2024 2024
Combining Gamma neuromodulation and robotic rehabilitation restores parvalbimin-mediated Gamma function and boosts motor recovery in stroke mice L Vignozzi, F Macchi, E Montagni, M Pasquini, A Martello, A Minetti, ... bioRxiv, 2024.08. 15.608060 , 2024 2024 Citations: 4
Investigating the synaptic mechanisms of the spread of wild type and P301S 1N4R human tau in in vitro and in vivo models C Panzi, L Restani, E Novelli, R Guarascio, M Cheetham, S Wray, ... Alzheimer's & Dementia 19, e072297 , 2023 2023
Molecular changes underlying decay of sensory responses and enhanced seizure propensity in peritumoral neurons E Tantillo, M Scalera, E De Santis, N Meneghetti, C Cerri, M Menicagli, ... Neuro-oncology 25 (8), 1463-1473 , 2023 2023 Citations: 7
Facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanus F Fabris, S Varani, M Tonellato, I Matak, P Šoštarić, P Meglić, M Caleo, ... JCI insight 8 (11), e166978 , 2023 2023 Citations: 10
Fast-spiking interneurons of the premotor cortex contribute to initiation and execution of spontaneous actions N Giordano, C Alia, L Fruzzetti, M Pasquini, G Palla, A Mazzoni, S Micera, ... Journal of Neuroscience 43 (23), 4234-4250 , 2023 2023 Citations: 19
Disruption of layer-specific visual processing in a model of focal neocortical epilepsy A Panarese, M Vissani, N Meneghetti, E Vannini, M Cracchiolo, S Micera, ... Cerebral Cortex 33 (7), 4173-4187 , 2023 2023 Citations: 5
Synaptic alterations in visual cortex reshape contrast-dependent gamma oscillations and inhibition-excitation ratio in a genetic mouse model of migraine N Meneghetti, C Cerri, E Vannini, E Tantillo, A Tottene, D Pietrobon, ... The journal of headache and pain 23 (1), 125 , 2022 2022 Citations: 18
Environmental enrichment counteracts the effects of glioma in primary visual cortex MA Di Castro, S Garofalo, E De Felice, N Meneghetti, E Di Pietro, ... Neurobiology of Disease 174, 105894 , 2022 2022 Citations: 7
Laminin 511 and WNT signalling sustain prolonged expansion of hiPSC-derived hippocampal progenitors K Dunville, F Tonelli, E Novelli, A Codino, V Massa, AM Frontino, S Galfrè, ... Development 149 (20), dev200353 , 2022 2022 Citations: 6
Criticality in neural network behavior and its implications for computational processing in healthy and perturbed conditions I Sandvig, A Sandvig Frontiers in Neural Circuits 16, 1041250 , 2022 2022
Modulatory Effects on the Spread of Pathological Tau by Botulinum Neurotoxins C Panzi, L Restani, E Novelli, R Guarascio, ME Cheetham, S Wray, ... Toxicon 214, S67-S68 , 2022 2022
Cortical Rewiring Following Peripheral Injection of Botulinum Neurotoxin Type A V Massa, A Tiberi, M Pirazzini, O Rossetto, M Caleo, L Restani Toxicon 214, S67 , 2022 2022
TETANUS NEUROTOXIN ACTS AT THE NEUROMUSCULAR JUNCTION AND ON BRAINSTEM CENTERS THAT CONTROL MUSCLE MOVEMENT, RESPIRATION AND SWALLOWING IN A MURINE MODEL OF CEPHALIC TETANUS F Fabris, S Varani, M Tonellato, I Matak, P Šoštarić, P Meglić, M Simonato, ... Pharmaca, 180-180 , 2022 2022
Dietary barley Β-D-glucan supplementation protects against heart-brain axis dysfunction in mice: a new approach of perioperative neuro/cardioprotection C Baroni, C Spalletti, J Agrimi, N Di Lascio, F Mastorci, AP Beltrami, ... JOURNAL OF ANESTHESIA, ANALGESIA AND CRITICAL CARE 2 (Supplement 1) , 2022 2022
MOST CITED SCHOLAR PUBLICATIONS
Brain‐derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment C Rossi, A Angelucci, L Costantin, C Braschi, M Mazzantini, F Babbini, ... European Journal of Neuroscience 24 (7), 1850-1856 , 2006 2006 Citations: 792
Long-distance retrograde effects of botulinum neurotoxin A F Antonucci, C Rossi, L Gianfranceschi, O Rossetto, M Caleo Journal of Neuroscience 28 (14), 3689-3696 , 2008 2008 Citations: 607
Microvesicles released from microglia stimulate synaptic activity via enhanced sphingolipid metabolism F Antonucci, E Turola, L Riganti, M Caleo, M Gabrielli, C Perrotta, ... The EMBO journal 31 (5), 1231-1240 , 2012 2012 Citations: 414
Neuroplastic changes following brain ischemia and their contribution to stroke recovery: novel approaches in neurorehabilitation C Alia, C Spalletti, S Lai, A Panarese, G Lamola, F Bertolucci, F Vallone, ... Frontiers in cellular neuroscience 11, 76 , 2017 2017 Citations: 349
Neuroinflammatory targets and treatments for epilepsy validated in experimental models E Aronica, S Bauer, Y Bozzi, M Caleo, R Dingledine, JA Gorter, ... Epilepsia 58, 27-38 , 2017 2017 Citations: 241
Botulinum neurotoxins A and E undergo retrograde axonal transport in primary motor neurons L Restani, F Giribaldi, M Manich, K Bercsenyi, G Menendez, O Rossetto, ... PLoS pathogens 8 (12), e1003087 , 2012 2012 Citations: 222
Evidence for anterograde transport and transcytosis of botulinum neurotoxin A (BoNT/A) L Restani, F Antonucci, L Gianfranceschi, C Rossi, O Rossetto, M Caleo Journal of Neuroscience 31 (44), 15650-15659 , 2011 2011 Citations: 199
Epilepsy as a neurodevelopmental disorder Y Bozzi, S Casarosa, M Caleo Frontiers in psychiatry 3, 19 , 2012 2012 Citations: 197
Ultra-high mass resolution MALDI imaging mass spectrometry of proteins and metabolites in a mouse model of glioblastoma M Dilillo, R Ait-Belkacem, C Esteve, D Pellegrini, S Nicolardi, M Costa, ... Scientific reports 7 (1), 603 , 2017 2017 Citations: 194
A radial glia-specific role of RhoA in double cortex formation S Cappello, CRJ Böhringer, M Bergami, KK Conzelmann, A Ghanem, ... Neuron 73 (5), 911-924 , 2012 2012 Citations: 191
Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study Scientific Reports 7 (1), 39471 , 2017 2017 Citations: 190
Advanced neurotechnologies for the restoration of motor function S Micera, M Caleo, C Chisari, FC Hummel, A Pedrocchi Neuron 105 (4), 604-620 , 2020 2020 Citations: 182
Synergistic effects of brain-derived neurotrophic factor and chondroitinase ABC on retinal fiber sprouting after denervation of the superior colliculus in adult rats D Tropea, M Caleo, L Maffei Journal of Neuroscience 23 (18), 7034-7044 , 2003 2003 Citations: 167
Brain-derived neurotrophic factor is an anterograde survival factor in the rat visual system M Caleo, E Menna, S Chierzi, MC Cenni, L Maffei Current biology 10 (19), 1155-1161 , 2000 2000 Citations: 159
Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP V Resta, E Novelli, G Vozzi, C Scarpa, M Caleo, A Ahluwalia, A Solini, ... European Journal of Neuroscience 25 (9), 2741-2754 , 2007 2007 Citations: 155
Early depolarizing GABA controls critical-period plasticity in the rat visual cortex G Deidda, M Allegra, C Cerri, S Naskar, G Bony, G Zunino, Y Bozzi, ... Nature neuroscience 18 (1), 87-96 , 2015 2015 Citations: 153
The chemokine CCL2 mediates the seizure-enhancing effects of systemic inflammation C Cerri, S Genovesi, M Allegra, F Pistillo, U Püntener, A Guglielmotti, ... Journal of Neuroscience 36 (13), 3777-3788 , 2016 2016 Citations: 138
Central effects of tetanus and botulinum neurotoxins M Caleo, G Schiavo Toxicon 54 (5), 593-599 , 2009 2009 Citations: 134
More than at the neuromuscular synapse: actions of botulinum neurotoxin A in the central nervous system R Mazzocchio, M Caleo The Neuroscientist 21 (1), 44-61 , 2015 2015 Citations: 132
Rehabilitation and plasticity following stroke: insights from rodent models M Caleo Neuroscience 311, 180-194 , 2015 2015 Citations: 123
