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Engineering brain activity patterns for therapeutics of neuropsychiatric and neurological disorders

Descripción del proyecto

Un enfoque innovador para administrar tratamientos en el encéfalo

Nuestra comprensión del encéfalo, la neuropsiquiatría y los trastornos neurológicos se ve limitada por la falta de métodos no invasivos para medir circuitos neuronales. El proyecto EngineeringBAP, financiado con fondos europeos, está trabajando en tecnologías innovadoras que permitirán mediciones a gran escala con una resolución de neurona única, así como la modulación de circuitos neuronales a través de la administración precisa de neuromoduladores. Para demostrar el principio, los científicos ya han corregido anormalidades encefálicas en peces cebra mutantes a través de la administración localizada de un cóctel neuromodulador. El trabajo ayudará a estudiar en detalle la actividad encefálica y caracterizará las disfunciones de los circuitos asociadas a trastornos neurológicos, con lo que allanará el camino para unos tratamientos mejorados.

Objetivo

Neuropsychiatric and neurological disorders are complex dysfunctions of neuronal circuits. Their treatment
has been limited by the lack of non-invasive methods for measuring the underlying circuit dysfunctions, and
for direct and localized modifications of these circuits. We propose minimally invasive technologies for
measuring brain activity and functional connectivity patterns, and for manipulating them directly in vivo to
correct the abnormal behavioural phenotypes (in rodents with potential scalability to non-human primates and
humans). First, we present a proof-of-principle study on mutant zebrafish, in which we correct whole-brain
level abnormal activity patterns and behaviours by using large-scale single-neuron resolution measurements,
and by simultaneously modulating multiple sub-networks via neuromodulator cocktails. Next, we present
strong preliminary data in rodents and our plan: (1) For manipulating brain circuits in rodents/primates noninvasively,
we will develop technologies that can deliver receptive-specific neuromodulators to spatially
precise brain targets without opening/damaging the blood brain barrier. These methods will employ engineered
ultrasound pulses and drug carrying microparticles we designed. (2) For reading out the brain circuits in
rodents/primates, we will develop flexible low-power neuromorphic μECoG circuits that can detect single
neuron signals from superficial cortical layers of many cortical areas simultaneously. (3) Finally, these novel
technologies will be comprehensively evaluated on a mouse model of obsessive compulsivity and anxiety
using a battery of behavioural tasks to reverse the pathological symptoms (beyond what is achievable by
existing approaches). This project constitutes a major step towards the development and testing of minimallyinvasive
and high-precision technologies for manipulating brain activity patterns, which can impact both our
understanding of the brain and treatment of intractable brain disorders.

Palabras clave

Régimen de financiación

ERC-COG - Consolidator Grant

Institución de acogida

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Aportación neta de la UEn
€ 1 998 984,00
Dirección
Raemistrasse 101
8092 Zuerich
Suiza

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Región
Schweiz/Suisse/Svizzera Zürich Zürich
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 1 998 984,00

Beneficiarios (1)