This unit investigates the cellular and molecular mechanisms involved in the fine-tuning of neuronal communication, and their consequences for plasticity, neuroprotection and cognition. The brain possesses substances that either enhance or depress communication between neurones, adjusting neuronal activity to specific needs. Our broad investigation goal is to elucidate how these substances interplay and how they are involved in diseases of the nervous system.

The Neurosciences Unit at IMM is composed of three research groups that focus on Neuromodulation and Plasticity, Neuroprotection, and Receptor Biology and Cognition. These research groups actively employ integrated approaches involving:
1) electrophysiology (recordings of synaptic currents and potentials),
2) neurochemistry (neurotransmitter release and uptake, molecular visualization at synapses), and
3) behaviour (learning, memory and anxiety tests in laboratory animals).

Neuromodulation and Plasticity – Devoted to understanding the mechanisms controlling neurotransmitter release and action at the synaptic level and their implications in neuronal plasticity and in brain dysfunctions.
Neuroprotection – devoted to investigating mechanisms involved in neuronal protection against common pathological insults, such as low oxygen, low glucose or neurodegenerative disease states, such as Alzheimer’s or Parkinson’s disease
Receptor Biology and Cognition – devoted to understanding the relationship between ageing mechanisms and pathological conditions that affect brain structures involved in memory and cognition, such as depression, anxiety, epilepsy, and neurodegenerative diseases.

National:
2010-2013 - Modulation of GABAergic transmission in the hippocampus by adenosine. Coordinator: Ana M Sebastião (FCT, PTDC/SAU-NMC/110838/2009)
2010/2013 – Cross talk between neurotrophic factor receptors (TrkB) and adenosine A2A receptors: implications for amyotrophic lateral sclerosis (ALS). (PTDC/SAU-NEU/101752/2008). Coordinator: J.A. Ribeiro
2010/2013 – Role of adenosine A2A receptors in chronic stress – implications for learning and memory (PTDC/SAU-NEU/099853/2008). Coordinator: L V Lopes
2007/2010 – Trophic actions of neurotrophic factors: dependency of co-activation of A2A adenosine receptors, FCT, Colllab: Centro Neurociências de Coimbra (Emília Duarte), Faculdade de Farmácia, Univ Lisboa (Rui Silva). Project coordinator: A.M. Sebastião. PTDC/SAU-NEU/64126/2006
2007/10 – Trophic actions of neurotrophic factors: dependency of co-activation of A2A adenosine receptors. FCT, PTDC/SAU-NEU/64126/2006. PI: AM Sebastião
2008/2011 – Membrane receptors and mediators involved in plastic changes induced by neuronal insults: implications for neuroprotection. (PTDC SAU-FCF 68607 2006). Coordinator: J.A. Ribeiro
2005/2009 - Interaction between endocannabinoids and adenosine in the hippocampus (FCT - POCTI/SAU-FCF/57973/2004). Coordinator: J.A. Ribeiro.
2005/2009 - Role of TrkB receptors in ageing (Gulbenkian Foundation JG/ Nº. 0494). Coordinator: J.A. Ribeiro.

International
Pending - Relationships Between Adenosine A2a Receptors and Glucocorticoids in Age-Related Hippocampal Dysfunctions Coordinator: L.V. Lopes, Programa Pessoa. Collaboration with David Blum, INSERM, Lille, France
2007/2010 – COST B30 European Science Foundation Action on Neural Regeneration and Plasticity (NEREPLAS).
2006/2009. Blockade of adenosine A2A receptors prevents protein phosphorylation in the striatum induced by cortical stimulation and interactions with galanin receptors. –. Coordinators: S. Ferre (NIH, Bethesda, USA) and J.A. Ribeiro (IMM) and R Franco (Univ Barcelona).
2008/2011 – Effect of neurotrophic factors on postnatal gut motility”” funded by NESTEC (NESTEC /474/2008). Coordinator: L V Lopes

To see our International Collaborations, click here

• Vasco C Sousa, Natália Assaife-Lopes, Joaquim A Ribeiro, Judith A Pratt, Ros R Brett and Ana M Sebastião (2010) Regulation of Hippocampal Cannabinoid CB1 Receptor Actions by Adenosine A1 Receptors and Chronic Caffeine Administration: Implications for the Effects of D9-Tetrahydrocannabinol on Spatial Memory. Neuropsychopharmacol.[Epub ahead of print]
• Sebastião AM, Assaife-Lopes N, Diógenes MJ, Vaz SH, Ribeiro JA. (2010)Modulation of brain-derived neurotrophic factor (BDNF) actions in the nervous system by adenosine A(2A) receptors and the role of lipid rafts. Biochim Biophys Acta. 2010 Jul 11. [Epub ahead of print]
• Assaife-Lopes N, Sousa VC, Pereira DB, Ribeiro JA, Chao MV, Sebastião AM (2010). Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts: implications for neuromodulation. J Neurosci. In the press
• Lopes, L.V., Sebastião, A.M. and Ribeiro, J.A. (2010). Adenosine and related drugs in brain diseases: present and future in clinical trials. Curr Topics Med Chem, in the press
• Sebastião AM (2010) Adenosine and epilepsy-thinking beyond A1 receptors. Purinergic Signal. 6:1-2.
• Ribeiro, J. A. and Sebastião A. M. (2010). Modulation and MetaModulation of Synapses by Adenosine. Acta Physiol 199, 161-169.
• Ribeiro J A and Sebastiao A M (2010). Caffeine and Adenosine. J Alzheim dis., 20, 3-13.
• Pousinha, P.A., Sebastião, A.M and Ribeiro, J.A. (2010). Predominance of adenosine excitatory over inhibitory effects on transmission at the neuromuscular junction of infant rats. J Pharmacol Exp Ther , 332:153-63 (accepted in 2009).
• Serpa, A., Ribeiro, J A and Sebastião, A M (2009). Cannabinoid CB1 and Adenosine A1 receptors independently inhibit hippocampal synaptic transmission. Eur J Pharmacol 623, 41-46.
• Sebastião AM and Ribeiro JA (2009). Tuning and Fine-tuning synapses with adenosine. Current Neuropharmacol, 7, 180-194.
• Cristóvão-Ferreira S, Vaz SH, Ribeiro JA, Sebastião AM (2009) Adenosine A2A receptors, through PKA activation, restrain PKC inhibition of GAT-1-mediated GABA uptake by nerve terminals. J Neurochem 109, 336-347.
• Fontinha BM, Delgado-García JM, Madroñaln, Ribeiro JA, Sebastião AM, Gruart A (2009). Adenosine A2A receptor modulation of hippocampal CA3-CA1 synapse plasticity during associative learning in behaving mice Neuropsychopharmacology 34:1865-1874 (
• Gomes CA, Simões PF, Canas PM, Quiroz C, Sebastião AM, Ferré S, Cunha RA, Ribeiro JA (2009). GDNF control of the glutamatergic cortico-striatal pathway requires tonic activation of adenosine A2A Receptors. J Neurochem. 108, 1208-1219.
• Sebastião AM, Ribeiro JA (2009) Triggering neurotrophic factor actions through adenosine A2A receptor activation: implications for neuroprotection. Br J Pharmacol 158: 15-22.
• Fontinha B.M., Ribeiro, J.A. & Sebastião, A.M. (2008). Enhancement of long –term potentiation by BDNF requires adenosine A2A receptor activation by endogenous adenosine Neuropharmacology, 54, 924-933.
• Quiroz C*, Gomes C*, Pak AC, Ribeiro JA, Goldberg SR, Hope BT, Ferre S. (2006). Blockade of adenosine A2A receptors prevents protein phosphorylation in the striatum induced by cortical stimulation. J Neurosci. 26:10808-10812 (*co-first authors)
• Cunha-Reis D, Fontinha B, Ribeiro JA, Sebastião AM (2007) Tonic adenosine A1 and A2A receptor activation is required for the excitatory action of VIP on synaptic transmission in the CA1 area of the hippocampus. Neuropharmacol 52, 313-320.
• Pousinha PA, Diogenes MJ, Ribeiro JA, et al. Triggering of BDNF facilitatory action on neuromuscular transmission by adenosine A(2A) receptors Neurosci. Letts 404, 143-147, 2006.
• Magalhaes-Cardoso MT, Pereira MF, Oliveira L, et al. Ecto-AMP deaminase blunts the ATP-derived adenosine A(2A) receptor facilitation of acetylcholine release at rat motor nerve endings .J. Physiol. Lond: 549, 399-408, 2003.
• Biber K*, Pinto-Duarte A*, Wittendorp MC, Dolga AM, Fernandes CC, Kunzel JVFD, Keijser JN, Devries R, Ijzerman AP, Ribeiro JA, Eisel U, Sebastião AM, Boddeke, GM. (2008). Interleukin-6 upregulates neuronal adenosine A1 receptors: implications for neuromodulation and neuroprotection. Neuropsychopharmacology 33, 2237–2250 (*co-first authors).
• Fernandes C, Pinto-Duarte A, Ribeiro JA, Sebastião AM (2008) Postsynaptic action of brain-derived neurotrophic factor attenuates alpha7 nicotinic acetylcholine receptor-mediated responses in hippocampal interneurons. J Neurosci 28, 5611-5618
• Diógenes MJ, Assaife-Lopes N, Pinto-Duarte A, Ribeiro JA, Sebastião AM (2007) Influence of age on BDNF modulation of hippocampal synaptic transmission: interplay with adenosine A2A receptors. Hippocampus, 17, 577-585.
• Pinto-Duarte A, Coelho JE, Cunha RA, Ribeiro JA, Sebastiao AM (2005) Adenosine A(2A) receptors control the extracellular levels of adenosine through modulation of nucleoside transporters activity in the rat hippocampus. J Neurochem, 93, 595-604
• Diógenes, M.J., Fernandes, C.C., Sebastião, A.M., Ribeiro, J.A. (2004) Activation of adenosine A2A receptor facilitates BDNF modulation of synaptic transmission in hippocampal slices. J. Neurosci. 24, 2905-2913.
• Rodrigues RJ, Canas PM, Lopes LV, Oliveira CR, Cunha RA (2008) Modification of adenosine modulation of acetylcholine release in the hippocampus of aged rats. Neurobiol Aging, 29, 1597-1601
• Chen JF, Sonsalla PK, Pedata F, Melani A, Domenici, MR, Popoli P, Geiger J, Lopes LV, de Mendonça A. (2007) Adenosine A2A receptors and brain injury: broad spectrum of neuroprotection, multifaceted actions and “fi ne tuning” modulation. Prog Neurobiol 83, 310-331

The Unit members are part of the Institute of Pharmacology and Neurosciences at the Faculty of Medicine, being involved in the following teaching areas:

Pre-graduate at FMUL
• Pharmacology in Organs and Systems Module, to Medical Students at 1st and 2nd years (1st semester)
• Pharmacology in Organs and Systems Module, to Medical Students at 3rd year (1st semester)
• Neuropharmacology in Neuroscience Module, to Medical Students at 2nd year (2nd Semester)
• Experimental Neuroscience Course (optional) to Medical Students at 3rd year (ist semester
• Tutorials on ‘Introduction to Biomedical Engeneering’ to students of the Biomedical Engeneering Course, 1st year, 1st semester

Master Courses
• Coordination of the Master Programme in Neuroscience, FMUL(other coordinators (Mamede de Carvalho and Isabel Pavão Martins, both IMM PIs)
• Molecular Neurobiology, Cellular Neurobiology, Basic Electrophysiology and Neuroethics Modules at the Master Course in Neuroscience, FMUL (1st semester)
• Neurochemistry to Master students at the Faculty of Sciences, University of Lisbon (FCUL), 2nd semester
• Neuroscience to students of the Master Course in Cognitive Sciences, University of Lisbon.

PhD Courses
• Coordination of the PhD Programme in Neuroscience, FMUL (other coordinators (Mamede de Carvalho and Isabel Pavão Martins, both IMM PIs)
• Molecular Neurobiology, Cellular Neurobiology, Basic Electrophysiology and Neuroethics Modules at the PhD Programme in Neuroscience, FMUL (1st semester)
• Neuroscience Module to students of the PhD Programme in Cognitive Sciences, University of Lisbon.

Public Understanding of Science Activities

Members of the Unit regularly participate in the Brain awareness Week, organizing debates, public seminars, sessions in schools (all levels, which includes a range of students from 4 to 17 years old), accepting invitations to TV and radio interviews.

Neurociências.pt

Sociedade Portuguesa de Neurociências

Sociedade Portuguesa de Farmacologia

Federation of European Neuroscience Societies

Society for Neurosciences

The Federation of European Pharmacological Societies

The DANA Foundation

Institute of Pharmacology and Neurosciences (IFN)
Instituto de Medicina Molecular
Av. Prof. Egas Moniz, EEM, piso 1B
1649-028 Lisboa
Portugal
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Tel. +351 21 798 5183
Fax. +351 21 799 9454