Layer-Specific fMRI Responses to Excitatory and Inhibitory Neuronal Activities in the Olfactory Bulb

High-resolution functional magnetic resonance imaging (fMRI) detects localized neuronal activity via the hemodynamic response, but it is unclear whether it accurately identifies neuronal activity specific to individual layers. To address this issue, we preferentially evoked neuronal activity in superficial, middle, and deep layers of the rat olfactory bulb: the glomerular layer by odor (5% amyl acetate), the external plexiform layer by electrical stimulation of the lateral olfactory tract (LOT), and the granule cell layer by electrical stimulation of the anterior commissure (AC), respectively. Electrophysiology, laser-Doppler flowmetry of cerebral blood flow (CBF), and blood oxygenation level-dependent (BOLD) and cerebral blood volume-weighted (CBV) fMRI at 9.4 T were performed independently. We found that excitation of inhibitory granule cells by stimulating LOT and AC decreased the spontaneous multi-unit activities of excitatory mitral cells and subsequently increased CBF, CBV, and BOLD signals. Odor stimulation also increased the hemodynamic responses. Furthermore, the greatest CBV fMRI responses were discretely separated into the same layers as the evoked neuronal activities for all three stimuli, whereas BOLD was poorly localized with some exception to the poststimulus undershoot. In addition, the temporal dynamics of the fMRI responses varied depending on the stimulation pathway, even within the same layer. These results indicate that the vasculature is regulated within individual layers and CBV fMRI has a higher fidelity to the evoked neuronal activity compared with BOLD. Our findings are significant for understanding the neuronal origin and spatial specificity of hemodynamic responses, especially for the interpretation of laminar-resolution fMRI.