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Laboratory of Cellular Basis of Behavior and Disease
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