Project description
An innovative approach for delivering brain therapeutics
Our understanding of the brain and of neuropsychiatric and neurological disorders is impeded by the lack of non-invasive methods for measuring neural circuits. The EU-funded EngineeringBAP project is working on innovative technologies that will allow large-scale single-neuron resolution measurements as well as the modulation of neural circuits through the precise delivery of neuromodulators. As a proof-of-principle, scientists have already corrected brain abnormalities in mutant zebrafish, through the localised delivery of a neuromodulator cocktail. The work will help study brain activity in detail and characterise the circuit dysfunctions associated with neurological disorders, thereby paving the way for improved treatments.
Objective
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.
Fields of science
Keywords
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
8092 Zuerich
Switzerland