Neurophysiology

Problem

Chronic or genetic diseases alter the role of neurons and glial cells, including alterations in their excitability and connectivity, which contribute to chronic pain and itch, mental retardation or other neurological disorders, including neurodegenerative diseases. However, most of the underlying mechanisms remain unknown. In order to develop the most appropriate and effective drugs and treatments, it is necessary to unravel the molecular and functional basis of such alterations and identify the specific proteins and signalling pathways that may be the most adequate therapeutic targets.

Approach

The group is interested in understanding the molecular and functional bases of neuronal excitability, neuron-glia crosstalk and communication between neurons in normal and pathological conditions.

In sensory neurons, we study which ion channels and receptors participate in the detection of painful and itchy stimuli, and how they are regulated during chronic pain and itch. In glutamatergic neurotransmission, we study the glutamate receptors and their regulatory proteins, as well as the functional consequences of de novo mutations altering ionotropic glutamate receptors. Finally, another research line of our group is studying the role of neuron-microglia crosstalk in synaptic and neuronal deficits in neurodegenerative diseases and other neurological disorders.

Impact

Our several ongoing projects investigate the molecular mechanisms underlying the alterations of membrane receptors or ion channels and their contribution to neurologic diseases, from migraine pain to chronic itch and from developmental encephalopathies (e.g., GRIN-related disorders) to neurodegeneration. As part of this quest, we have: 1) identified a family of potassium channels in sensory neurons that regulate electrical activity and whose alteration is associated with neuropathic or migraine pain, 2) identified different factors that regulate microglial phagocytosis of neurons and synapses in neurodegeneration, and 3) comprehensively delineated GRIN-related disorders, and developed pioneer personalised treatments (i.e., preclinical and clinical trial) for this rare developmental encephalopathy.

Besides understanding the molecular mechanisms involved in the different neurological disorders abovementioned, our goal is to identify and validate specific molecular targets and develop new specific drugs that could open new therapeutic avenues for the treatment of different neurological disorders.

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