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Laboratory of Cellular Basis of Behavior and Disease

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Neuroglia basis of behavioral processes

Edgar Soria-Gómez

Endocannabinoids and neuroglial cells

Susana Mato

My research lines focus on the description of brain circuits responsible of behavioral processes in males and females. Our interest is to identify cell-type specific mechanisms responsible of cognitive- and emotional-related behaviors. In particular, we use the cannabinoid receptor type-1 (CB1) as a tool to study complex brain functions. One of my lines of research is devoted to the study of the functional interaction of the endocannabinoid and cholinergic systems at different levels, from genetics to behavior. Specifically, this project aims at understanding the physiological basis of memory processes with the ultimate goal of developing therapeutic approaches to treat neurodegenerative diseases. A second research line of my group focuses on the study of emotional states, which occur as a result of an orchestrated body activity. In the brain, different structures participate in the processing of emotional information. Among them, the medial habenula (MHb) is critically positioned as an interface between brain regions coding aversive signals and areas regulating emotional responses. Moreover, the MHb is a sub-ventricular structure hosting a great variety of specialized cells: tanycyte-like cells, mast cells, astrocytes, and different neuronal phenotypes. Furthermore, the neighboring vasculature possesses increased transport function, evoking sensitivity to peripheral modulators of brain functions. However, the functional link between specific MHb cell types, peripheral signals and a given pathophysiological process is unknown. We propose that the MHb cellular milieu is a perfect candidate to study the influence of peripheral signals on the pathophysiology of emotional responses.

Techniques

  • Behavioral tasks (cognition and emotion)
  • Stereotaxic techniques
  • Viral vectors and pharmacogenetics (DREADDs)
  • In vivo electrophysiology, fiber photometry, and optogenetics in freely moving mice
  • Immunofluorescence confocal microscopy

The CB1 receptors are heterogeneously expressed in neurons and glial cells and profile as a therapeutic tool to tackle a variety of neurological disorders including demyelinating conditions. However, clinical success has been limited and major questions concerning cannabinoid signaling remain unsolved particularly with regard to their role as modulators of glial cells (Bernal-Chico et al., Glia 2022). The aim of my lab is to decipher how cannabinoid CB1 receptors in glial cells – mainly astrocytes and oligodendrocytes – tune the cellular processes that govern myelin pathophysiology in the context of demyelinating and neurodevelopmental diseases. By combining in vivo, ex vivo and in vitro approaches, genetic mouse models, human stem cell technology and patient-derived samples, we aim at identifying the molecular hallmarks of CB1 receptor-mediated signaling in glial cells and their impact on neuronal network function. Our ultimate goal is to provide novel insights on the clinical relevance of targeting neuroglial CB1 receptors to treat demyelination and genetic neurodevelopmental disorders.

Techniques

  • Primary cultures of neuroglial cells
  • Culture and differentiation of human induced-pluripotent stem cells (hiPSC)
  • In vivo models of myelin pathology and neurodevelopmental disorders
  • Fluorescent-activated cell sorting
  • Viral vectors and pharmacogenetics (DREADDs)
  • Imaging of calcium and lactate indicators in cultured cells, brain slices and freely moving mice
  • Ex vivo electrophysiology
  • Immunofluorescence confocal microscopy

People

Latest publications

  1. Aging and the social-emotional brain

    Soria-Gómez, Edgar; Piriz, Joaquín; Torres-Alemán, Ignacio
    Frontiers in Aging Neuroscience (May, 2024) DOI: 10.3389/fnagi.2024.1417410
  2. Spatial organization of neuron–astrocyte interactions in the somatosensory cortex

    Baraibar, Andrés M; Belisle, Lindsey; Marsicano, Giovanni; Matute, Carlos; Mato, Susana; Araque, Alfonso; Kofuji, Paulo
    Cerebral Cortex (Apr, 2023) DOI: 10.1093/cercor/bhac357
  3. Cannabinoid CB1 receptor expression in oligodendrocyte progenitors of the hippocampus revealed by the NG2-EYFP-knockin mouse

    Manterola, A.; Chara, J.C.; Aguado, T.; Palazuelos, J.; Matute, C.; Mato, S.
    Frontiers in Neuroanatomy (Oct, 2022) DOI: 10.3389/fnana.2022.1030060
  4. Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice

    Sánchez-de la Torre, Aníbal; Aguado, Tania; Huerga-Gómez, Alba; Santamaría, Silvia; Gentile, Antonietta; Chara, Juan Carlos; Matute, Carlos; Monory, Krisztina; Mato, Susana; Guzmán, Manuel; Lutz, Beat; Galve-Roperh, Ismael; Palazuelos, Javier
    Cell Death & Disease (Jul, 2022) DOI: 10.1038/s41419-022-05032-z
  5. Cannabinoid control of hippocampal functions: The where matters

    Robledo‐Menendez, Almudena; Vella, Maria; Grandes, Pedro; Soria‐Gomez, Edgar
    The FEBS Journal (Apr, 2022) DOI: 10.1111/febs.15907
  6. Endocannabinoid signaling in brain diseases: Emerging relevance of glial cells

    Bernal-Chico, Ana; Tepavcevic, Vanja; Manterola, Andrea; Utrilla, Carmen; Matute, Carlos; Mato, Susana
    Glia (Mar, 2022) DOI: 10.1002/glia.24172
  7. Fit-for-purpose based testing and validation of antibodies to amino- and carboxy-terminal domains of cannabinoid receptor 1

    Echeazarra, Leyre; García del Caño, Gontzal; Barrondo, Sergio; González-Burguera, Imanol; Saumell-Esnaola, Miquel; Aretxabala, Xabier; López de Jesús, Maider; Borrega-Román, Leire; Mato, Susana; Ledent, Catherine; Matute, Carlos; Goicolea, María Aranzazu; Sallés, Joan
    Histochemistry and Cell Biology (Aug, 2021) DOI: 10.1007/s00418-021-02025-5
  8. Environmental Enrichment Rescues Endocannabinoid-Dependent Synaptic Plasticity Lost in Young Adult Male Mice after Ethanol Exposure during Adolescence

    Rico-Barrio, Irantzu; Peñasco, Sara; Lekunberri, Leire; Serrano, Maitane; Egaña-Huguet, Jon; Mimenza, Amaia; Soria-Gomez, Edgar; Ramos, Almudena; Buceta, Ianire; Gerrikagoitia, Inmaculada; Mendizabal-Zubiaga, Juan; Elezgarai, Izaskun; Puente, Nagore; Grandes, Pedro
    Biomedicines (Jul, 2021) DOI: 10.3390/biomedicines9070825
  9. Δ9-Tetrahydrocannabinol promotes functional remyelination in the mouse brain

    Aguado, Tania; Huerga-Gómez, Alba; Torre, Aníbal Sánchez-de la; Resel, Eva; Chara, Juan Carlos; Matute, Carlos; Mato, Susana; Galve-Roperh, Ismael; Guzman, Manuel; Palazuelos, Javier
    British Journal of Pharmacology (Jul, 2021) DOI: 10.1111/bph.15608
  10. Δ9-Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo

    Huerga‐Gómez, Alba; Aguado, Tania; Torre, Aníbal Sánchez-de la; Bernal‐Chico, Ana; Matute, Carlos; Mato, Susana; Guzmán, Manuel; Galve‐Roperh, Ismael; Palazuelos, Javier
    Glia (Mar, 2021) DOI: 10.1002/glia.23911