Neuronal Mechanisms Mediating Long-Lasting Changes in Signal Processing Also Influence Neurovascular Coupling in the...

To investigate how altered neural signal processing influences functional magnetic resonance imaging (fMRI)-blood oxygenation level-dependent (BOLD) responses in the hippocampus, we performed simultaneous in vivo electrophysiology and BOLD-fMRI in male Wistar rats during electrical stimulation of the perforant pathway. By defining input activity via applied pulses and measuring output activity through population spikes, we were able to identify qualitative and quantitative changes in signal processing once the relationship between input and output changed. An initial series of three low-intensity stimulations (LIS) induced clear, consistent BOLD responses. However, following a high-intensity stimulation (HIS) that triggered brief neuronal after-discharges, a subsequent series of three identical LIS resulted in significantly attenuated BOLD responses. Electrophysiological data revealed that while total neuronal activity remained stable across all LIS, only the initial LIS induced long-lasting changes in signal processing (persisting beyond 1 min) and transiently increased gamma-band activity. In contrast, after HIS, these changes were reversed and could no longer be reinduced, coinciding with the absence of further increases in gamma-band activity. Pharmacological experiments using MK801 and isoflurane further demonstrated that the mechanisms underlying long-lasting changes in signal processing also enhance LIS-induced BOLD responses. These findings suggest that positive fMRI-BOLD responses reflect functionally relevant changes in neural network properties-such as long-lasting modifications in signal processing-rather than simple increases in total neuronal output.