FINE TUNING SYNAPTIC PLASTICITY AND EXCITABILITY
(@ NEUROSCIENCES AND PHARMACOLOGY)
Endogenous modulators of synaptic activity, such as adenosine, endocannabinoids, and serotonin, play a central role in regulating brain function. Their signaling can also be perturbed by exogenous molecules including caffeine, THC analogues, or LSD analogues. By investigating these modulators and their interactions, the group aims to identify synaptic targets of novel molecules with potential therapeutic applications as antiseizure medications or antidepressants.
The group focuses on GABAergic, glutamatergic, and serotonergic transmission in healthy rodents and in animal models of epilepsy or depression, using ex vivo brain tissue. A major goal is to understand the mechanisms of action underlying the control of synaptic excitability and plasticity, and to determine how these mechanisms relate to putative therapeutic roles. In collaboration with the Biochemistry group, drug effects on blood–brain barrier permeability are also being addressed. Transcriptomic and proteomic alterations are explored through collaborations with other national groups or by outsourcing.
At the in vivo level, the group evaluates behavioral outcomes including memory, anxiety, depression-like states, and locomotion. In collaboration with the Physiology group, cardiovascular outcomes are also being investigated.
RESEARCH TEAM
Sebastião, Ana, PhD
GROUP LEADER
Ana M. Sebastião obtained her degree in Biology from the Faculty of Sciences, University of Lisbon, in 1982, her PhD in Cell Physiology from the Faculty of Sciences and Technology, New University of Lisbon, in 1987, and her Habilitation in Neuroscience from the Faculty of Medicine, University of Lisbon, in 2002. After a period (1986–1997) as a researcher at the Gulbenkian Institute of Science, she joined (1987) the Faculty of Medicine, University of Lisbon, where she is currently Full Professor.
She served as President of the Portuguese Society for Pharmacology (2000–2003), as President of the Portuguese Society for Neuroscience (2003–2007), of which she was a founding member (1993), and as an elected member of the Federation of European Pharmacological Societies (2002–2008). She is also a member of the coordination teams of Master’s and PhD programmes at the Faculty of Medicine, University of Lisbon, and has directly supervised 18 PhD students.
She served as Director of the Mind-Brain College of the University of Lisbon (2015–2018), having been part of its proponent team (2014). She has published over 250 full papers, cited in more than 7,250 articles (excluding self-citations).
ORCID: 0000-0001-9030-6115
E-mail: anaseb@medicina.ulisboa.pt
Erkizia-Santamaria, Inês, PhD
Postdoc Researcher
Ines graduated in Pharmacy (University of the Basque Country UPV/EHU, 2019), and completed her PhD on the mechanism of action and antidepressant effects of psilocybin (2024). Her research focuses on finding the neurobiological mechanisms involved in psychiatric illnesses, in particular, mood disorders, with the long-term goal to find new pharmacological tools to ameliorate their treatment. As such, she employs in vivo (animal models of psychiatric disorders, behavioural assessments, brain microdialysis, neuroimaging), ex vivo (electrophysiology) and in vitro techniques.
ORCID: 0000-0002-6163-4571
E-mail: iesantamaria@medicina.ulisboa.pt
Gonçalves-Ribeiro, Joana, PhD
Postdoc Researcher
Joana graduated in Biochemistry from the Faculty of Sciences, University of Lisbon (Portugal), in 2016. She obtained her Master’s degree in Molecular Biology and Genetics from the same institution in 2018, and in 2025 completed her PhD in Biomedical Sciences (Neurosciences specialization) at the Faculty of Medicine, University of Lisbon. Her doctoral research focused on the role of astrocytic CB1 receptors in synaptic plasticity and depressive-like behavior, in collaboration with the University of Minnesota (Prof. Alfonso Araque) and the University of Barcelona (Dr. Gemma Navarro).
Joana has broad expertise in in vitro techniques (neuronal cultures, neuroblastoma cell lines, western blotting, immunofluorescence), ex vivo approaches (brain dissection and region isolation, electrophysiology including extracellular and patch-clamp recordings), as well as in vivo procedures (animal handling and experimental procedures).
ORCID: 0000-0002-5194-6512
E-mail: jgribeiro@medicina.ulisboa.pt
Lima da Silva, Gabriela Larissa, MSc
Phd student
Gabriela graduated in Biomedical Sciences from São Paulo State University “Júlio de Mesquita Filho” (UNESP, Botucatu, Brazil). She obtained her Master’s degree in General and Applied Biology from the same institution and is currently a PhD candidate at the Botucatu School of Medicine (FMB-UNESP, Brazil). As part of her doctoral training, she is undertaking a research internship at the Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon (Lisbon, Portugal). Her research focuses on cognition in Rattus norvegicus, with particular emphasis on memory processes and the meso-cortico-limbic circuit across different experimental paradigms, including the developmental origins of health and disease (DOHaD), sleep deprivation, and pharmacology. She has expertise in transcardiac perfusion, brain dissection and regional isolation, immunohistochemistry, transcriptomics, biochemical analyses, behavioural assessments, and experimental animal handling protocols. In addition to her academic work, Gabriela is actively engaged in science communication, coordinating Brazilian outreach projects such as Bando Siriema (science theatre) and the Podcast Puro Acaso. She is also committed to promoting scientific education and open science, having conceived and coordinated the project Abertamente Científico, focused on reproducibility and open science practices, alongside participation in other academic and cultural initiatives.
ORCID: 0000-0002-5142-401X
Email: gabrielalarissa@medicina.ulisboa.pt
Sales Garcia, Cristian, BSc
MSc Student
Cristian graduated in Biochemistry (Grinnell College, USA) in 2023, after which he became a NeuroData Erasmus Mundus scholar pursuing a double degree master’s in Brain and Data Science/Biomedical Engineering. He is currently developing his master’s thesis for the Instituto Superior Técnico at the Neuron-Glia Lab (FMUL-CCUL), under the supervision of Sandra Vaz. The main topic of his research is absence epilepsy and its commorbidities, in which he balances neurophysiology and behavioral techniques with data science. In an attempt to facilitate research, he is developing an open-source, automated seizure detection algorithm to use on recordings of the Genetic Absence Epilepsy Rats from Strasbourg.
Santos-Lopes, André, BSc
MSc Student in Neurosciences
André Santos-Lopes is a second-year MSc student in Neurosciences at the Faculty of Medicine, University of Lisbon, where he is currently conducting his master’s thesis within the Institute of Pharmacology and Neurosciences. He obtained his BSc in Biology from the Instituto Superior de Agronomia, University of Lisbon. His master’s research focuses on targeting the cannabinoid system and adenosine A2A receptors to alleviate chemotherapy-induced neuropathic pain. His scientific interests include pain mechanisms, the cannabinoid system, the adenosine system, and health sciences. Methodologically, his work involves in vivo animal behaviour studies, intraperitoneal drug administration in rats, and molecular and histological techniques such as immunohistochemistry, Western blot, ELISA, and PCR.
E-mail: andre-lopes1@medicina.ulisboa.pt
Simões-Estevão, Diogo, BSc
MSc Student
Diogo Simões-Estêvão is a second-year MSc student in Neurosciences at the Faculty of Medicine, University of Lisbon, where he is affiliated with the Institute of Pharmacology and Neuroscience. He earned his BSc in Psychology from the Faculty of Psychology, University of Lisbon. His master’s thesis investigates the effects of psilocybin on hippocampal synaptic plasticity and metaplasticity, with a particular focus on dose- and time-dependent mechanisms. His research aims to elucidate the underlying biological mechanisms driving these plasticity changes. Diogo’s scientific interests center on the effects of psilocybin and other classic psychedelics on the brain, particularly in the context of psychiatric disorders and consciousness. Methodologically, his work involves in vivo compound administration in mice, brain dissection, and electrophysiological techniques.
INTERNATIONAL COLLABORATORS
Kenneth Jacobson, NIDDKD, NIH, Bethesda, USA.
Zsolt Lenkei, Institute of Psychiatry and Neuroscience of Paris, France.
Tomáš Páleníček, Prague Psychiatric Center, Czech.
Eleonora Palma and Gabrielle Ruffolo, Sapienza University of Rome, Italy.
RECENT PROJECTS
International:
2020-2023: Epileptogenesis and Epilepsy Network: from genes, synapses and circuitries to pave the way for novel drugs and strategies (EpiEpiNet). Twinning action between the University of Lisbon, University of Lund, University of Rome, and University of Amsterdam. Financed by H2020-WIDESPREAD-05-2017-Twinning (EpiEpinet) (grant agreement No. 952455). Coordinator: AM Sebastião. ENDED
National:
2022-2025: Does context matter for drug action? Contextual dependency of the long-lasting neurobiological and antidepressant actions of psilocybin. Financed by Fundação para a Ciência e Tecnologia, Portugal (PTDC/MED-FAR/4834/2021). Coordinator: A.M. Sebastião. WILL END SOON
(to start soon): A novel target for disease-selective antiseizure drug. Accepted by FCT.
SELECTED PUBLICATIONS
Farinha-Ferreira, M., Miranda-Lourenço, C., Galipeau, C., Lenkei, Z., & Sebastião, A. M. (2025). Concurrent stress modulates the acute and post-acute effects of psilocybin in a sex-dependent manner. Neuropharmacology, 266, 110280. https://doi.org/10.1016/j.neuropharm.2024.110280
Ghosh, A., Ribeiro-Rodrigues, L., Ruffolo, G., Alfano, V., Domingos, C., Rei, N., Tosh, D. K., Rombo, D. M., Morais, T. P., Valente, C. A., Xapelli, S., Bordadágua, B., Rainha-Campos, A., Bentes, C., Aronica, E., Diógenes, M. J., Vaz, S. H., Ribeiro, J. A., Palma, E., Jacobson, K. A., … Sebastião, A. M. (2024). Selective modulation of epileptic tissue by an adenosine A3 receptor-activating drug. British journal of pharmacology, 181(24), 5041–5061. https://doi.org/10.1111/bph.17319
Sebastião, A. M., & Ribeiro, J. A. (2023). Adjusting the brakes to adjust neuronal activity: Adenosinergic modulation of GABAergic transmission. Neuropharmacology, 236, 109600.. https://doi.org/10.1016/j.neuropharm.2023.109600
Farinha-Ferreira, M., Rei, N., Fonseca-Gomes, J., Miranda-Lourenço, C., Serrão, P., Vaz, S. H., Gomes, J. I., Martins, V., de Alves Pereira, B., & Sebastião, A. M. (2022). Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior. Neuropharmacology, 214, 109155. https://doi.org/10.1016/j.neuropharm.2022.109155