Calcium-sensitive functional Magnetic Resonance Imaging as a breakthrough technique to follow brain-wide intracellular calcium dynamics defining multi-scale neuronal activity

Projektbeschreibung

Neuronale Aktivität im Gehirn mit Kalzium sichtbar machen

Kalzium ist ein zuverlässiger Marker für neuronale Aktivität. Die Kalzium-Bildgebung könnte daher wichtige neue Informationen über das Netzwerk Gehirn und seine Funktionsweise liefern. Mit den bisher gängigen Methoden lässt sich die Kalziumdynamik aber nicht im großen Maßstab messen. BrainwideNeuroCaSens, eine EU-finanzierte Initiative, will einen neuen Kalzium-Biosensor entwickeln, der in der funktionellen Magnetresonanztomografie zum Einsatz kommen kann. Dieser Biosensor reagiert auf Kalzium und trägt zur Visualisierung von neuronaler Aktivität bei, die in sonst unzugänglich tief gelegenen Strukturen und großen Regionen von Säugetiergehirnen auftritt. Das neu entwickelte Instrument kann zur Erforschung von neuronalen Schaltkreisen im gesamten gesunden oder von neurodegenerativen Erkrankungen befallenen Gehirn dienen.

Ziel

Neuroscience’s ultimate goal of achieving a holistic understanding of brain function requires a cross-scale integration from single-cell physiology to global network topology. While remarkable achievements towards this goal have been made, brain research faces the challenge of incorporating molecular and cellular neurobiology into the context of macro-scale network activation. Calcium is a reliable marker of neural activity and calcium imaging is among the most widely used methods in modern biology, although the technology for measuring large-scale calcium dynamics remains limited. BrainwideNeuroCaSens seeks to pioneer magnetic calcium-responsive sensors in the context of functional magnetic resonance imaging (fMRI) as a tool for a brain-wide interrogation of neural systems, providing an order of magnitude speed increase and a neurophysiologically precise readout, thereby far surpassing other noninvasive neuroimaging methods. These magnetic calcium-responsive sensors with physicochemical properties similar to optical imaging dyes, make use of the whole-brain, noninvasive imaging capabilities of fMRI and allow to detect translationally relevant, molecular precise correlates of neuronal activity in otherwise inaccessible deep structures and large regions of the mammalian brain. While focusing on dynamic functional connectivity relationships to study stimulus-responses and intrinsic network dynamics, the proposed experiments have significance for understanding brain-wide neural circuits in health and disease, offering pre-clinical potential for neurodegenerative pathologies. BrainwideNeuroCaSens’ offers a molecular precise readout of global neural network function and thereby opens the possibility for therapeutic strategies aiming at a restoration of network disruptions, for example in but not limited to, Alzheimer’s disease. BrainwideNeuroCaSens will bring the next-generation imaging technique of molecular fMRI to the EU and make the applicant pioneer in this field.