Massimo Avoli
Massimo Avoli (born July 13, 1951) is a Canadian/Italian neuroscientist who has made valuable contributions to the field of the fundamental mechanisms underlying epileptic disorders.
| Massimo Avoli | |
|---|---|
 MassimoAvoli.jpg | |
| Born | July 13, 1951 Rome, Italy |
| 💼 Occupation | |
| Known for | Role of the inhibitory neurotransmitter GABA in the generation of focal interictal and ictal discharges |
Education and Career
Avoli was born and grew up in Rome, Italy, where he attended the Sapienza University of Rome from 1969 to 1979, first to obtain an MD degree (1975) and then a Neurology specialty degree (1979) under the supervision of Dr. Mario Manfredi. During these years, he began to be interested in the fundamental mechanisms of epileptiform synchronization in the neurophysiology laboratory of Dr. Aldo Brancati.
In 1979, Avoli moved to Canada to work at the Montreal Neurological Institute and Hospital (the Neuro) of McGill University under the supervision of Dr. Pierre Gloor, who had been a pupil of Dr. Herbert Jasper; there, in 1982, he obtained a PhD working on the thalamocortical mechanisms sustaining generalized absence seizures. After graduating from McGill University, in 1983, Avoli did a postdoctoral stint in Dr. Per Andersen’s laboratory at the University of Oslo, Norway, to learn the application of the in vitro brain slice preparation for analyzing the fundamental mechanisms underlying focal epileptic disorders in human and rodent brains. Dr. Andersen’s laboratory, where long term potentiation of synaptic transmission had been discovered a few years earlier.[1], had turned into an “obligatory stop” for several young neuroscientists who would later apply the in vitro brain slice preparation to analyze the mechanisms regulating neural excitability and epileptiform synchronization. To just mention a few: Drs. Philip Schwartzkroin, Raymond Dingledine, John Habliz, and Jean-Claude Lacaille.
Since 1983 Avoli served as Assistant Professor (to become Full Professor in 1994) in the Department of Neurology and Neurosurgery of the Faculty of Medicine at McGill University. In 2001 he was called for Chiara Fama by the Sapienza University of Rome where he worked as part-time Professor of Physiology until 2021.
Research and Work
Avoli’s early research (1979-1984) at the Neuro, focused on the contribution of thalamus and neocortex in the generation of generalized spike and wave discharges, an EEG pattern that is the hallmark of absence seizures in humans. His work, performed in collaboration with Dr. George Kostopoulos in Dr. Gloor’s laboratory, demonstrated that interactions between interconnected cortical and thalamic networks are required for the occurrence of generalized spike and wave discharges; accordingly, either thalamus or cortex per se could not generate such generalized epileptic activity[2].
Upon his return from Oslo in 1983, Avoli also begun to analyze the role of the inhibitory neurotransmitter GABA in the generation of focal interictal and ictal discharges in rodent and human brain slices in vitro. In the 1980s, weakening of inhibition was considered the main mechanism leading to focal interictal and ictal discharges, and thus to epileptic disorders. A turning point in Avoli’s studies was his visit to the laboratory of Dr. Daniel Johnston at Baylor College in Houston, Texas. There, in vitro experiments were performed by employing the K+ channel blocker 4-aminopyridine (4AP), a convulsant that increases the presynaptic release of both excitatory and inhibitory neurotransmitters[3]. Back to Montreal, Avoli discovered that brain slices maintained in vitro, when treated with 4-aminopyridine (4AP), generate a specific type of slow interictal spike that (i) is mainly contributed by GABA-mediated inhibitory currents[4]; and (ii) precedes (and thus it may initiate) seizure-like electrographic events[5]. Successive work performed in collaboration with Dr. Mary Morris (University of Ottawa, Canada), Dr. Rüdiger Köhling (University of Mũnster, Germany), Dr. Marco de Curtis (Besta Neurological Institute in Milan, Italy) as well as with Drs. René Pumain and Jacques Louvel (INSERM, Paris, France) revealed that the main mechanism for these slow interictal spikes to induce seizure-like events rests on synchronous interneuron firing leading to excessive activation of postsynaptic GABAA receptors that, in turn, causes sizeable increases in extracellular [K+] [6] [7] through the activation of the KCC2 co-transporter[8]. It was indeed well known that elevating extracellular [K+] induces neuronal hyperexcitability along with seizure activity[9]. Therefore, Avoli’s studies firmly identified a paradoxical role of GABAA signaling in initiating - and perhaps sustaining - focal seizures characterized at onset by the occurrence of a sentinel spike followed by low-amplitude, high-frequency EEG activity, so-called low-voltage fast (LVF) onset seizures[10].
Around 2010, Avoli’s work was extended to in vivo models of mesial temporal lobe epilepsy such as those induced by an initial status epilepticus caused by systemic injection of pilocarpine or kainic acid. In these experiments, which were performed in collaboration with Drs. Maxime Levesque, attention was often directed to the relation between pathological high-frequency oscillations (HFOs, 80-500 Hz) and the occurrence of interictal spikes and focal seizures. HFOs are categorized as (i) ripples (80-200 Hz) - which may represent population IPSPs generated by principal neurons entrained by synchronously active GABAergic interneuron - and (ii) fast ripples (250-500 Hz) that may mirror the abnormally synchronous firing of principal cells [11][12]. Avoli’s experiments demonstrated that progression from interictal to ictal activity in LVF onset seizures is characterized by higher ripple rates compared to fast ripples; in contrast, interictal to ictal discharge transition in seizures with hypersynchronous (HYP) onset [9] - which coincides with a series of focal spikes at a frequency of approx. 2Hz - is associated to higher fast ripple compared to ripple rates. Moreover, during ictal activity, ripples predominate in LVF while fast ripples prevail in HYP onset seizures[13]. The specific involvement of interneurons and principal cells in LVF and HYP onset seizures, respectively, was also confirmed in successive in vivo and in vitro experiments employing the optogenetic stimulation of interneurons or principal cells; these studies demonstrated that LVF onset seizures are induced by optogenetic activation of interneurons while those induced by the optogenetic activation of principal cells have a HYP onset pattern [14][15][16].
Avoli’s most recent studies have focused on catamenial epilepsy that is characterized by increased seizure frequency or severity during specific phases of the menstrual cycle. Results obtained in Avoli’s laboratory from in vivo and in vitro experiments in rodents have shown that parvalbumin-positive interneurons in cortical structures become hyperexcitable during the periovulatory phase (i.e., in coincidence with proestrus/estrus when estrogen blood levels are high), thus playing a role in worsening seizures in this specific type of catamenial epilepsy [17][18]
Awards and Honors
In 1987, Avoli received the Korrespondierenden Mitglied of the German League against Epilepsy and a recognition as member of the Neurologia Italiana nel Mondo from the Istituto Neurologico C. Besta and the Italian National Research Council. In 1991 he was named Ontario-Quebec Neuroscience Lecturer and in 1995 he was awarded the Stiftung Michael Prize for Epilepsy Research. In 2017, he received the Wilder Penfield Award from the Canadian League Against Epilepsy, in 2021 the Basic Research in Epilepsy Award from the American Epilepsy Society, and in 2022 the Premio Venezia from the Chambre de Commerce Italienne au Canada for collaborative studies between the Neuro of McGill University and the Istituto Neurologico Carlo Besta. In 2023 Avoli became Professore Onorario at the Faculty of Medicine, Sapienza University of Rome, Italy.
Personal life
Avoli is married with Alfonsa Martelli and has two daughters, Chiara and Emanuela. Avoli was an avid, intermediate skier and tennis player until knee problems stopped these hobbies. He likes to paint and he is a fan of the Irish singer/composer Van Morrison.
References
- ↑ Bliss, T. V. P.; Lømo, T. (July 1973). "Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path". The Journal of Physiology. 232 (2): 331–356. Bibcode:1973JPhsg.232..331B. doi:10.1113/jphysiol.1973.sp010273. ISSN 0022-3751. PMC 1350458. PMID 4727084.
- ↑ Avoli, Massimo (May 2012). "A brief history on the oscillating roles of thalamus and cortex in absence seizures". Epilepsia. 53 (5): 779–789. doi:10.1111/j.1528-1167.2012.03421.x. ISSN 0013-9580. PMC 4878899. PMID 22360294.
- ↑ Buckle, P J; Haas, H L (May 1982). "Enhancement of synaptic transmission by 4-aminopyridine in hippocampal slices of the rat". The Journal of Physiology. 326 (1): 109–122. doi:10.1113/jphysiol.1982.sp014180. ISSN 0022-3751. PMC 1251462. PMID 6286946.
- ↑ Perreault, P.; Avoli, M. (1989-05-01). "Effects of low concentrations of 4-aminopyridine on CA1 pyramidal cells of the hippocampus". Journal of Neurophysiology. 61 (5): 953–970. doi:10.1152/jn.1989.61.5.953. ISSN 0022-3077. PMID 2566657.
- ↑ Avoli, M.; Psarropoulou, C.; Tancredi, V.; Fueta, Y. (1993-09-01). "On the synchronous activity induced by 4-aminopyridine in the CA3 subfield of juvenile rat hippocampus". Journal of Neurophysiology. 70 (3): 1018–1029. doi:10.1152/jn.1993.70.3.1018. ISSN 0022-3077. PMID 7901344.
- ↑ D'Antuono, M.; Louvel, J.; Kohling, R.; Mattia, D.; Bernasconi, A.; Olivier, A.; Turak, B.; Devaux, A.; Pumain, R.; Avoli, M. (2004-07-01). "GABAA receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex". Brain. 127 (7): 1626–1640. doi:10.1093/brain/awh181. ISSN 0006-8950. PMID 15175227.
- ↑ Avoli, Massimo; Chen, Li-Yuan; Di Cristo, Graziella; Librizzi, Laura; Scalmani, Paolo; Shiri, Zahra; Uva, Laura; de Curtis, Marco; Lévesque, Maxime (May 2023). "Ligand-gated mechanisms leading to ictogenesis in focal epileptic disorders". Neurobiology of Disease. 180. doi:10.1016/j.nbd.2023.106097. PMID 36967064 Check
|pmid=value (help). Unknown parameter|article-number=ignored (help) - ↑ Kaila, Kai; Trevelyan, Andrew; Raimondo, Joseph; Ala-Kurikka, Tommi; Huberfeld, Gilles; Avoli, Massimo; de Curtis, Marco (May 2024), Noebels, Jeffrey L.; Avoli, Massimo; Rogawski, Michael A.; Vezzani, Annamaria, eds., "GABAA-Receptor Signaling and Ionic Plasticity in the Generation and Spread of Seizures", Jasper's Basic Mechanisms of the Epilepsies (5 ed.), Oxford University PressNew York, pp. 111–142, doi:10.1093/med/9780197549469.003.0006, ISBN 978-0-19-754946-9, PMID 39637123 Check
|pmid=value (help), retrieved 2026-02-25 - ↑ Zuckermann, Emil C.; Glaser, Gilbert H. (January 1968). "Hippocampal epileptic activity induced by localized ventricular perfusion with high-potassium cerebrospinal fluid". Experimental Neurology. 20 (1): 87–110. doi:10.1016/0014-4886(68)90126-X. PMID 5637118.
- ↑ Velascol, Ana Luisa; Wilson, Charles L.; Babb, Thomas L.; Engel Jr, Jerome (January 2000). "Functional and Anatomic Correlates of Two Frequently Observed Temporal Lobe Seizure-Onset Patterns". Neural Plasticity. 7 (1–2): 49–63. doi:10.1155/NP.2000.49. ISSN 2090-5904. PMC 2565365. PMID 10709214.
- ↑ Jefferys, John G.R.; Menendez de la Prida, Liset; Wendling, Fabrice; Bragin, Anatol; Avoli, Massimo; Timofeev, Igor; Lopes da Silva, Fernando H. (September 2012). "Mechanisms of physiological and epileptic HFO generation". Progress in Neurobiology. 98 (3): 250–264. doi:10.1016/j.pneurobio.2012.02.005. PMC 4873284. PMID 22420980.
- ↑ Jiruska, Premysl; Alvarado-Rojas, Catalina; Schevon, Catherine A.; Staba, Richard; Stacey, William; Wendling, Fabrice; Avoli, Massimo (August 2017). "Update on the mechanisms and roles of high-frequency oscillations in seizures and epileptic disorders". Epilepsia. 58 (8): 1330–1339. doi:10.1111/epi.13830. ISSN 0013-9580. PMC 5554080. PMID 28681378.
- ↑ Lévesque, Maxime; Salami, Pariya; Gotman, Jean; Avoli, Massimo (2012-09-19). "Two Seizure-Onset Types Reveal Specific Patterns of High-Frequency Oscillations in a Model of Temporal Lobe Epilepsy". The Journal of Neuroscience. 32 (38): 13264–13272. doi:10.1523/JNEUROSCI.5086-11.2012. ISSN 0270-6474. PMC 4878898. PMID 22993442.
- ↑ Shiri, Zahra; Manseau, Frédéric; Lévesque, Maxime; Williams, Sylvain; Avoli, Massimo (March 2016). "Activation of specific neuronal networks leads to different seizure onset types". Annals of Neurology. 79 (3): 354–365. doi:10.1002/ana.24570. ISSN 0364-5134. PMC 4878884. PMID 26605509.
- ↑ Lévesque, Maxime; Chen, Li-Yuan; Etter, Guillaume; Shiri, Zahra; Wang, Siyan; Williams, Sylvain; Avoli, Massimo (November 2019). "Paradoxical effects of optogenetic stimulation in mesial temporal lobe epilepsy". Annals of Neurology. 86 (5): 714–728. doi:10.1002/ana.25572. ISSN 0364-5134. PMID 31393618.
- ↑ Wang, Siyan; Lévesque, Maxime; Fisher, Teddy A. J.; Kennedy, Timothy E.; Avoli, Massimo (2023-10-01). "CA3 principal cell activation triggers hypersynchronous-onset seizures in a mouse model of mesial temporal lobe epilepsy". Journal of Neurophysiology. 130 (4): 1041–1052. doi:10.1152/jn.00244.2023. ISSN 0022-3077. PMID 37703488 Check
|pmid=value (help). - ↑ Li, Fei Ran; Wang, Siyan; Suarez, Camila Franco; Lévesque, Maxime; Avoli, Massimo (September 2025). "Interneurons, GABAA signaling and their presumptive role in catamenial epilepsy". Neuroscience & Biobehavioral Reviews. 176. doi:10.1016/j.neubiorev.2025.106291. PMID 40669526 Check
|pmid=value (help). Unknown parameter|article-number=ignored (help) - ↑ Li, Fei Ran; Lévesque, Maxime; Wang, Siyan; Avoli, Massimo (March 2026). "Influence of the estrous cycle on seizure activity in a model of mesial temporal lobe epilepsy". Experimental Neurology. 397. doi:10.1016/j.expneurol.2025.115597. PMID 41391534 Check
|pmid=value (help). Unknown parameter|article-number=ignored (help)
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