Brain Circuits and Neuron-glia Adaptations
The Brain Circuits and Neuron-Glia Adaptations (C2B) team studies the mechanisms underlying mood, cognition, and motivation in physiological and pathological contexts. Using state-of-the-art technological platforms, our team combines basic, translational, and clinical research via an academia-industry productive partnership.
Our team develops studies from molecules to cells (neurons, glia), to circuits (anatomic and functional), to behavior (normal and maladaptive), in order to understand the basis of mood, cognition, and motivation. The fundamental neuroscience studies developed by our team set the basis to better understand the pathophysiological mechanisms of neurological/neuropsychiatric disorders such as addiction, depression and Alzheimer’s disease, in both preclinical models and humans.
In parallel, our clinical research studies explore novel neuroimaging and molecular biomarkers and therapeutic approaches in Major Depression and Treatment Resistant Depression with observational neuroimaging studies in clinical populations and clinical trials with new antidepressant molecules while our recent translational work focuses on the biomarker potential of exosomes.
This bidirectional scientific pipeline between fundamental and clinical neuroscience constitutes the key element that will enable this team to achieve the ambitious objectives of translating our ground-breaking scientific results about the cellular and circuit brain machinery to the clinical context, developing innovative therapeutic strategies to be tested in real-world clinical populations and create value and intellectual property in partnership with strategic partners in the industry.
Scientific excellence, Clinical impact, Innovation, Outreach activities for the society
Fundamental Neuroscience: Our team was awarded with an ERC Consolidator grant to investigate how valence is encoded in our brain and how this information leads to rewarding and aversive outcomes;
Clinical Research: We have currently running one Phase 1 Clinical Trial “A Randomised, Double-blind, Placebo-controlled Crossover EEG Study to Investigate the effect of GT-002 in Healthy Subjects” in 2CA-Braga – Industry Promoter: Gabather;
Entrepreneurship: We created one start-up company BNML – Behavioral & Molecular Lab, Lda, which uses advanced analytical methods to assess the therapeutic potential of new compounds at the behavioral, cellular, and molecular level, using animal models that mimic the symptoms of human disease.
Selected Research Outputs
Loureiro-Campos, E., Mateus-Pinheiro, A., Patrício, P., Soares-Cunha, C., Silva. J., Sardinha, V.M., Mendes-Pinheiro, B., Silveira-Rosa, T., Domingues, A.V., Rodrigues, A.J., Oliveira, J.F., Sousa, N., Alves, N.D.* and Pinto, L.* (2021). Constitutive AP2gamma deficiency reduces postnatal hippocampal neurogenesis, inducing anxious-like phenotype and memory impairments in juvenile mice that either persist or emerge during adulthood. eLife, 10:e70685. doi: 10.7554/eLife.70685.
Mateus-Pinheiro, A., Patrício, P., Alves, N.D., Martins-Macedo, J., Caetano, I., Silveira-Rosa, T., Araújo, B., Mateus-Pinheiro, M., Silva-Correia, J., Sardinha, V.M., Loureiro-Campos, E., Rodrigues, A.J., Oliveira, J.F., Bessa, J.M., Sousa, N., Pinto, L.* (2021). Hippocampal cytogenesis abrogation impairs inter-regional communication between the hippocampus and prefrontal cortex and promotes the time-dependent manifestation of emotional and cognitive deﬁcits. Molecular Psychiatry, Sep 14. doi: 10.1038/s41380-021-01287-8
Coimbra B, Soares-Cunha C, Vasconcelos NAP, Domingues AV, Borges S, Sousa N*, Rodrigues AJ* (2019). Role of laterodorsal tegmentum projections to nucleus accumbens in reward-related behaviors. Nat Commun 10, 4138. https://doi.org/10.1038/s41467-019-11557-3
Soares-Cunha C, de Vasconcelos NAP, Coimbra B, Domingues AV, Silva JM, Loureiro-Campos E, Gaspar R, Sotiropoulos I, Sousa N*, Rodrigues AJ* (2019). Nucleus accumbens medium spiny neurons subtypes signal both reward and aversion. Mol Psychiatry Dec;25(12):3241-3255. doi: 10.1038/s41380-019-0484-3.
Morais M, Patrício P, Mateus-Pinheiro A, Alves ND, Machado-Santos AR, Correia JS, Pereira J, Pinto L, Sousa N, Bessa JM*. (2017). The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression. Transl Psychiatry. Jun 6;7(6):e1146. doi: 10.1038/tp.2017.120.
Vieira R, Coelho A, Reis J, Portugal-Nunes C, Magalhães R, Ferreira S, Moreira PS, Sousa N, Bessa JM*. (2021). White Matter Microstructure Alterations Associated With Paroxetine Treatment Response in Major Depression. Front Behav Neurosci. Jul 22;15:693109. doi: 10.3389/fnbeh.2021.693109.
Silva J, Rodrigues S, Sampaio-Marques B, Gomes P, Neves-Carvalho A, Dioli C, Soares-Cunha C, Takashima A, Ludovico P, Wolozin B, Sousa N, Sotiropoulos I*. (2019). Dysregulation of autophagy and Stress granule-related proteins in stress-driven Tau pathology. Cell Death Diff. Aug;26(8):1411-1427. doi: 10.1038/s41418-018-0217-1.
Monteiro-Fernandes D, Silva JM, Soares-Cunha C, Dalla C, Kokras N, François A, Billiras R, Bretin S, Sousa N, Sotiropoulos I*. (2020). Allosteric modulation of AMPA receptors counteracts Tau-related excitotoxic synaptic signaling and memory deficits in Stress and Aβ-evoked hippocampal pathology. Molecular Psychiatry May 28. doi: 10.1038/s41380-020-0794-5.
Guerra-Gomes S, Cunha-Garcia D, Marques Nascimento DS, Duarte-Silva S, Loureiro-Campos E, Morais Sardinha V, Viana JF, Sousa N, Maciel P, Pinto L, Oliveira JF*. (2021). IP 3 R2 null mice display a normal acquisition of somatic and neurological development milestones. Eur J Neurosci. Sep;54(5):5673-5686. doi: 10.1111/ejn.14724.
Sardinha VM, Guerra-Gomes S, Caetano I, Tavares G, Martins M, Reis JS, Correia JS, Teixeira-Castro A, Pinto L, Sousa N, Oliveira JF (2017) Astrocytic signaling supports hippocampal–prefrontal theta synchronization and cognitive function. Glia 65:1944–1960.