Description du projet
Une approche innovante pour délivrer des traitements cérébraux
Notre compréhension du cerveau et des troubles neuropsychiatriques et neurologiques est freinée par le manque de méthodes non-invasives permettant de mesurer les circuits neuronaux. Le projet EngineeringBAP, financé par l’UE, travaille sur des technologies innovantes permettant de réaliser des mesures à la résolution du neurone individuel et à grande échelle, ainsi que de moduler les circuits neuronaux par le biais de l’administration précise de neuromodulateurs. En guise de démonstration de principe, les scientifiques ont déjà corrigé les anomalies cérébrales du poisson-zèbre mutant, en administrant localement un cocktail de neuromodulateurs. Ces travaux aideront à étudier l’activité cérébrale en détails et à caractériser les dysfonctionnements des circuits associés aux troubles neurologiques, ouvrant ainsi la voie à des traitements améliorés.
Objectif
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.
Champ scientifique
Mots‑clés
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
8092 Zuerich
Suisse