Pr Albrecht STROH (Institute of Pathophysiology, University Medical Center, and Leibniz Institute for Resilience Research, Mainz, Germany) has given a talk on Monday 27, February.
Short abstract:
All neuronal networks are imbued with the ability to homeostatically regulate their physiological activity states to maintain functionality. A fundamental question is to understand how and when neuronal networks dissociate from their physiological state to become pathological, which is ultimately manifested in form of a neurological disorder. Neural networks can undergo fundamental changes very early without a clear pathophysiological manifestation even in regions not yet affected by the underlying molecular and cellular pathophysiology. Neuronal networks aim for the maintenance of network stability at all cost in a primarily selfish and also individual manner. These stable network states are often associated with hyperactive neurons, marking the starting point for activity-dependent neurodegeneration. Using 2-photon calcium imaging in awake rodents, we identified these early neuronal network changes in visual cortical networks, yet we need to resolve brain-wide effects. BOLD fMRI provides a brain-wide and read-out capable of monitoring the effects of early disease on large-scale network signatures. Importantly, it represents a critical translational bridge, as fMRI can be conducted both in rodents and in humans. However, it does not directly report neuronal activity, but changes in blood flow and blood volume only associated to neuronal activity by neurovascular coupling. Consequently, fMRI alone does not unambiguously allow for the quantitative assessment of neuronal activity. In the last years, we established the combination of fMRI with optic-fiber-based calcium recordings, directly reporting local neuronal activity. This crossmodal approach may serve as a bridge between neurophysiological assessments of signatures of disease and brain wide assessments by fMRI. With these advances, identifying early – selfish – neural network state transitions may represent a distinct new therapeutic target for preventing the manifestation of disease and for fostering resilience.