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Dissecting the biophysical mechanisms of deep brain stimulation using voltage fluorescence microscopy

Project description

Mechanistic insight into deep brain stimulation

Deep brain stimulation (DBS) is a medical treatment that involves the use of a surgically implanted device to deliver electrical impulses to specific areas in the brain. It is primarily used to alleviate symptoms in individuals with certain neurological and psychiatric disorders, but its mechanisms are not fully understood. Funded by the European Research Council, the OptoDBS project aims to address challenges in studying DBS through an in vivo voltage fluorescence optical technique. The study will be performed in a mouse epilepsy model and involve the direct recording of membrane voltage in awake animals. OptoDBS will investigate the cellular mechanisms behind therapeutic effects of DBS in reducing seizures.

Objective

Deep brain stimulation (DBS) is a promising neuromodulation technique for the treatment of neurological and psychiatric diseases. DBS electrically stimulates brain tissue via implanted electrodes. However, the biophysical and therapeutic mechanisms underlying DBS remain largely unknown. While long-standing theories suggest that DBS suppresses neurons, subsequent studies have shown that DBS activates neurons via direct axonal excitation modulating membrane dynamics, information transfer, and network synchronization. Unfortunately, this conundrum has been difficult to resolve experimentally because of (1) the electrical interference occurring in electrode-based recordings and (2) the challenge of measuring cellular-level membrane voltage dynamics in the awake brain.
In this proposal, I will overcome for the first time both key challenges by using a novel in-vivo voltage fluorescence optical technique that permits the direct recording of the membrane voltage from identified neurons in awake animals, free of electrical interference. I will combine voltage fluorescence microscopy and electrical stimulation in a mouse model of epilepsy to optically dissect the cellular mechanisms underlying therapeutic DBS for reducing seizures in the limbic system.
This innovative and comprehensive approach will provide novel insights into the cellular and circuit processes occurring during DBS in the awake epileptic brain. This research program will provide an unprecedented opportunity to build a mechanistic framework of DBS and stimulation parameter selection with the ultimate goal of identifying more effective and targeted DBS protocols for human patients.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-STG

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Host institution

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 498 729,75
Address
DR MOLEWATERPLEIN 40
3015 GD Rotterdam
Netherlands

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 498 729,75

Beneficiaries (1)

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