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Research Departments >Functional and Systems Neurobiology department > Neurobiology Of The Basal Ganglia> Research Report

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Neurobiology Of The Basal Ganglia

My group is interested in the neurobiology of the basal ganglia, the anatomical substrate of Parkinson disease and drug addiction. Our research focus on the study of the molecular mechanisms of dopamine degeneration and in L-DOPA-induced dyskinesias, the two major challenges of Parkinson disease. Our goal is to understand the pathogenesis of the disease and to stop the degenerative process.

To address this, we are using transgenic animal models and patient-specific cellular models of Parkinson disease in combination with sophisticated genetic tools that allows us to interrogate and selectively manipulate at will, specific neurons in the striatum and in the dopaminergic system to see their role in dyskinesias and in the degeneration process.

Our work has established the main role of striatal direct pathway neurons in dyskinesias, and the ultrastructural and synaptic plasticity involved, as well as the contribution of each dopamine receptors.

In the research line of drug addiction, we have established the dopamine degeneration caused by design drugs of abuse such as methamphetamine and ecstasy as well as the main molecular mechanisms involved.

Research lines:

  1. To study the main molecular mechanisms involved in L-DOPA-induced dyskinesias:
    • Specific contribution of direct and indirect striatal projection neurons in dyskinesias
    • Mechanisms of dendritic spine remodelling and synaptic plasticity in Parkinson’s disease and in dyskinesia
  2. To study the mechanisms involved in the dopaminergic degeneration and neuronal vulnerability in Parkinson’s disease: Ethiology of PD.
    • Genetic and/or lesioned induced murine models of PD
    • Generation of patient-specific cellular models of PD derived from induced pluripotent stem cells (iPSC): To study cell biology and to carry out cell therapy (in collaboration with C. Vicario).
  3. To stablished the main molecular basis of methamphetamine addiction and of the dopamine toxicity induced by methamphetamine use.
    • Adolescence methamphetamine abuse a possible risk of PD
    • Role of glia cell in methamphetamine addiction and in the dopaminergic neurotoxic effects

Current methodology in the lab:

  • Behavioral motor tests, learning and memory tests, conditional place preference, sensitization, etc.
  • Immunicytochemnistry, in situ hybridization
  • Various genetic and chemical murine models of PD
  • Electrophysiology in brain slices with Patch clamp and voltage clamp techniques
  • Optogenetic with channel rhodopsins to stimulate or to inhibit selective neruons with laser
  • Pharmacogenetic with DREADDs activated with CNO
  • Cell cultures from fibroblasts of PD patients

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