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H2020Individual fellowship2015–2017

OPTOFRAX · Optopharmacological brain mapping of autism mouse models

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2015-07-01 → 2017-06-30
EU contribution
€170,122
Participants
1
Scheme
MSCA-IF-EF-RI

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Results in brief

Optopharmacological brain mapping of autism mouse models

The OPTOFRAX project aims at developing the seeds for a totally new therapeutic method for neurological disorders. Current pharmacological treatments suffer from known limitations: when a patient takes a drug, it distributes throughout the whole organism, including sick regions and healthy regions of the body, and usually at the same concentration everywhere. If one could deliver a drug only to the sick tissue and could adjust its concentration locally, many side effects would be avoided. Optopharmacology is a new promising technology that could achieve this goal. It is based on the development of photo-regulated drugs: molecules that can be activated or inactivated with light, so that its action can be finely controlled in space and time. These drugs could be activated only in the sick tissue with a flash of light, and only during the desired amount of time. In this line, our experiments pretended to test novel optopharmacological tools to control neuronal physiology with light. The first objective was to test modulators of glutamate receptors in brain slices and to demonstrate that we can control neuronal activity with rapid flashes of light. The second objective was to use this technique to map the known therapeutic effect of a photoswitchable inhibitor of the metabotropic glutamate receptors in an animal model of one autism spectrum disorder, the Fragile X syndrome. We wanted to test these drugs at different levels of resolution of the neuronal system: at a macroscale resolution (whole-brain level) and at microscale resolution (single-synapse level). Overall, this project was a proof-of-concept test for pre-clinical studies on the use of light-regulated drugs for neurological disorders.

Data: CORDIS, © European Union

Project objective

Manipulation of neurons with light-regulated proteins and drugs has opened unprecedented possibilities for phototherapies for neurological diseases. The host laboratory has developed a powerful new optopharmacological tool: a selective photoswitchable modulator of metabotropic glutamate receptors (mGluR). This drug can be activated or inactivated with light so that its action can be finely patterned in space and time. We aim at developing a novel application for this optical tool: a brain functional mapping technique. We will test it at two different levels of resolution. First, we will map the therapeutic site of action at whole-brain level. Inhibition of mGluR is a promising therapeutic strategy for autism disorders, including Fragile X, but the brain region responsible for this effect is not known. We will inactivate the drug locally by illuminating specific regions of the brain and will identify which region is the target for the therapeutic effect. Second, we will map the physiological contribution of mGluR to neuronal plasticity at the minimal spatial resolution: the individual synapse. Activation of mGluR induces long-term synaptic depression at the level of neurons, but it is unknown if it is also true at the level of single synapses. We will inactivate the drug in a single synapse using laser light and will test whether this specific synapse undergoes structural depression. This project will prove the utility of optopharmacological tools to map the therapeutic and phyisological mGluR function. This original approach could open countless possibilities for scientific, medical, and commercial applications. The project is an excellent opportunity for the Researcher to further develop his knowledge and to position him in unique multidisciplinary environment that will foster his career progression towards independence. At the same time, the Researcher’s experience acquired at MIT will be extremely valuable for the host institution and the European Research Area.

Original text from CORDIS.

Participants

  • FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA · BarcelonaCoordinatorSpain

Links

Data: CORDIS, © European Union