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Laboratory of Ultrastructural and Functional Neuroanatomy of the Synapse

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RESEARCH

The main research interest of our laboratory is to understand the interactions between the endocannabinoid system with excitatory and inhibitory systems controlling neuronal circuits recruited in the physiological processing of high brain functions. Cannabinoid receptors play important roles in the functioning of the central nervous system, the normal and pathological brain ageing as well as in the development and initiation of abnormal behaviours and brain disorders. Therefore, our final goal is to gain knowledge about how disruption of neural circuits leads to disease conditions. In particular, we are focused on the molecular organization of the components integrating the endocannabinoid system, and on the study of the anatomical and functional interplays between this system and classical membrane receptors at excitatory and inhibitory synapses in key brain regions involved in stress, addiction and epilepsy. Also, we are committed to the comprehensive characterization of neural ion channel and receptor kinetics in the brain, by focusing on the anatomical and functional characterization of the cannabinoid CB1 receptors in astrocytes and in mitochondria (mtCB1R) of brain cells. Because of the importance of CB1 receptors, this knowledge is essential for obtaining a realistic and accurate model of the brain.

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PROGRAMMES

APPROACHES

We have developed an interdisciplinary strategy combining electrophysiological, pharmacological and anatomical techniques applied to brain tissue of wild-type and genetically modified mice, and also to lesion-generated animal models of brain diseases.

TECHNIQUES

The methods used and handled efficiently in the laboratory are: High resolution immunoelectron microscopy; Electrophysiology ex vivo in brain slices (extracellular field recordings and patch-clamp); Immunocytochemistry for conventional light and confocal microscopy; Tract-tracing; Behavioural tests; Organotypic cultures.

Latest publications

  1. Omega-3 Recovers Cannabinoid 1 Receptor Expression in the Adult Mouse Brain after Adolescent Binge Drinking

    Martín-Llorente, Ane; Serrano, Maitane; Bonilla-Del Río, Itziar; Lekunberri, Leire; Ocerin, Garazi; Puente, Nagore; Ramos, Almudena; Rico-Barrio, Irantzu; Gerrikagoitia, Inmaculada; Grandes, Pedro
    International Journal of Molecular Sciences (Dec, 2023) DOI: 10.3390/ijms242417316
  2. Altered glial expression of the cannabinoid 1 receptor in the subiculum of a mouse model of Alzheimer's disease

    Terradillos, Itziar; Bonilla-Del Río, Itziar; Puente, Nagore; Serrano, Maitane; Mimenza, Amaia; Lekunberri, Leire; Anaut-Lusar, Ilazki; Reguero, Leire; Gerrikagoitia, Inmaculada; Ruiz de Martín Esteban, Samuel; Hillard, Cecilia J.; Grande, María T.; Romero, Julián; Elezgarai, Izaskun; Grandes, Pedro
    Glia (Apr, 2023) DOI: 10.1002/glia.24312
  3. Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus

    Lutzu, S.; Alviña, K.; Puente, N.; Grandes, P.; Castillo, P.E.
    Frontiers in Cellular Neuroscience (Apr, 2023) DOI: 10.3389/fncel.2023.1068472
  4. The effect of omega-3 fatty acids on alcohol-induced damage

    Serrano, Maitane; Rico-Barrio, Irantzu; Grandes, Pedro
    Frontiers in Nutrition (Apr, 2023)
  5. Differential Subcellular Distribution and Release Dynamics of Cotransmitted Cholinergic and GABAergic Synaptic Inputs Modify Dopaminergic Neuronal Excitability

    Gratiet, Keyrian Louis Le; Anderson, Christopher K.; Puente, Nagore; Grandes, Pedro; Copas, Charlotte; Nahirney, Patrick C.; Delaney, Kerry R.; Nashmi, Raad
    Journal of Neuroscience (Nov, 2022) DOI: 10.1523/JNEUROSCI.2514-21.2022
  6. Up-regulation of CB1 cannabinoid receptors located at glutamatergic terminals in the medial prefrontal cortex of the obese Zucker rat

    Echeazarra, Leyre; Barrondo, Sergio; García del Caño, Gontzal; Bonilla-Del Río, Itziar; Egaña-Huguet, Jon; Puente, Nagore; Aretxabala, Xabier; Montaña, Mario; López de Jesús, Maider; González-Burguera, Imanol; Saumell-Esnaola, Miquel; Goicolea, María Aránzazu; Grandes, Pedro; Sallés, Joan
    Frontiers in Neuroanatomy (Oct, 2022) DOI: 10.3389/fnana.2022.1004702
  7. GLAST versus GFAP as astroglial marker for the subcellular study of cannabinoid CB1 receptors in astrocytes

    Achicallende, Svein; Bonilla-Del Río, Itziar; Serrano, Maitane; Mimenza, Amaia; Lekunberri, Leire; Anaut-Lusar, Ilazki; Puente, Nagore; Gerrikagoitia, Inmaculada; Grandes, Pedro
    Histochemistry and Cell Biology (Jul, 2022) DOI: 10.1007/s00418-022-02139-4
  8. Cannabinoid CB2 Receptors Modulate Microglia Function and Amyloid Dynamics in a Mouse Model of Alzheimer’s Disease

    Ruiz de Martín Esteban, Samuel; Benito-Cuesta, Irene; [...] Grande, M. Teresa; Romero, Julián
    Frontiers in Pharmacology (Apr, 2022) DOI: 10.3389/fphar.2022.841766
  9. 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
  10. The endocannabinoid system in glial cells and their profitable interactions to treat epilepsy: Evidence from animal models

    Egaña-Huguet, J.; Soria-Gómez, E.; Grandes, P.
    International Journal of Molecular Sciences (Dec, 2021) DOI: 10.3390/ijms222413231