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Sensing activity-induced cell swellings and ensuing neurotransmitter releases for in-vivo functional imaging sans hemodynamics

Objective

Functional-Magnetic Resonance Imaging (fMRI) has transformed our understanding of brain function due to its ability to noninvasively tag ‘active’ brain regions. Nevertheless, fMRI only detects neural activity indirectly, by relying on slow hemodynamic couplings whose relationships with underlying neural activity are not fully known.
We have recently pioneered two unique MR approaches: Non-Uniform Oscillating-Gradient Spin-Echo (NOGSE) MRI and Relaxation Enhanced MR Spectroscopy (RE MRS). NOGSE-MRI is an exquisite microstructural probe, sensing cell sizes (l) with an unprecedented l^6 sensitivity (compared to l^2 in conventional approaches); RE MRS is a new spectral technique capable of recording metabolic signals with extraordinary fidelity at ultrahigh fields.
This proposal aims to harness these novel concepts for mapping neural activity directly, without relying on hemodynamics. The specific objectives of this proposal are:
(1) Mapping neural activity via sensing cell swellings upon activity (μfMRI): we hypothesize that NOGSE can robustly sense subtle changes in cellular microstructure upon neural firings and hence convey neural activity directly.
(2) Probing the nature of elicited activity via detection of neurotransmitter release: we posit that RE MRS is sufficiently sensitive to robustly detect changes in Glutamate and GABA signals upon activation.
(3) Network mapping in optogenetically-stimulated, behaving mice: we propose to couple our novel approaches with optogenetics to resolve neural correlates of behavior in awake, behaving mice.
Simulations for μfMRI predict >4% signal changes upon subtle cell swellings; further, our in vivo RE MRS experiments have detected metabolites with SNR>50 in only 6 seconds. Hence, these two complementary –and importantly, hemodynamics-independent– approaches will represent a true paradigm shift: from indirect detection of neurovasculature couplings towards direct and noninvasive mapping of neural activity in vivo.

Field of science

  • /natural sciences/chemical sciences/analytical chemistry/spectroscopy

Call for proposal

ERC-2015-STG
See other projects for this call

Funding Scheme

ERC-STG - Starting Grant

Host institution

FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Address
Avenida Brasilia, Centro De Investigacao Da Fundacao Champalimaud
1400-038 Lisboa
Portugal
Activity type
Research Organisations
EU contribution
€ 1 787 500

Beneficiaries (1)

FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Portugal
EU contribution
€ 1 787 500
Address
Avenida Brasilia, Centro De Investigacao Da Fundacao Champalimaud
1400-038 Lisboa
Activity type
Research Organisations