Brain active transmembrane water cycling measured by MR isassociated with neuronal activity.

Abstract

fMRI is widely used to study brain activity. Unfortunately, conventional fMRI methods assess neuronal activity only indirectly, through hemodynamic coupling. Here, we show that active, steady-state transmembrane water cycling (AWC) could serve as a basis for a potential fMRI mechanism for direct neuronal activity detection. AWC and neuronal actitivity in rat organotypic cortical cultures were simultaneously measured with ahybrid MR-fluorescence system. Perfusion with a paramagnetic MRI contrast agent, Gadoteridol, allows NMR determination of the kinetics of transcytolemmal water exchange. Changes in intracellular calcium concentration, [Cai2+ ] were used as a proxy of neuronal activity and were monitored by fluorescence imaging. When we alter neuronal activity by titrating with extracellular [K+ ] near thenormal value, we see an AWC response resembling Na+ -K+ -ATPase (NKA) Michaelis-Menten behavior. When we treat with thevoltage-gated sodium channel inhibitor, or with an excitatory postsynaptic inhibitor cocktail, we see AWC decrease by up to 71%. AWC was found also to be positively correlated with the basal level of spontaneous activity, which varies in different cultures. These results suggest that AWC is associated with neuronal activity and NKA activity is amajor contributor in coupling AWC to neuronal activity. Although AWC comprises steady-state, homeostatic transmembrane water exchange, our analysis also yields a simultaneous measure of the average cell volume, which reports any slower nettransmembrane water transport.