The role of ongoing neuronal activity for baseline and stimulus-induced BOLD signals in the rat hippocampus

To understand how ongoing neuronal activity affects baseline BOLD signals, neuronal and resultant fMRI responses were simultaneously recorded in the right hippocampus of male rats during continuous low-frequency (2 or 4 Hz) pulse stimulation of the right perforant pathway. Despite continuously increased neuronal activity, BOLD signals only transiently increased in the hippocampus and subsequently returned to either the initial level (2 Hz) or even to a consistently lower level (4 Hz). Whereas the initially transient increase in BOLD signals coincided with an increased spiking of granule cells, the subsequent reduction of BOLD signals was independent of granule cell spiking activity but coincided with persistent inhibition of granule cell excitability, i.e., with reduced post-synaptic activity and prolonged population spike latency. The decline in BOLD signals occurred in the presence of an elevated local cerebral blood volume (CBV), thus the reduction of granule cell excitability is attended by high oxygen consumption. When previous or current stimulations lessen baseline BOLD signals, subsequent short stimulation periods only elicited attenuated BOLD responses, even when actual spiking activity of granule cells was similar. Thus, the quality of stimulus-induced BOLD responses critically depends on the current existing inhibitory activity, which closely relates to baseline BOLD signals. Thus, a meaningful interpretation of stimulus-induced BOLD responses should consider slowly developing variations in baseline BOLD signals; therefore, baseline correction tools should be cautiously used for fMRI data analysis.