The actual intrinsic excitability of granular cells determines the ruling neurovascular coupling mechanism in the rat dentate gyrus

Paired-pulse stimulation of the perforant pathway was used to study the relation between granular cell activity and the resultant fMRI response in the rat dentate gyrus. By varying the interpulse interval (IPI), paired-pulse stimulations caused: a depression (20 ms IPI), a facilitation (100 ms IPI), a mixture of depression and facilitation (30 ms IPI), or no change (500 ms IPS) in the second response. Eight identical paired pulses were applied during one stimulation train and the evoked field potentials and generated fMRI responses were measured simultaneously. Application of consecutive stimulation trains caused time-dependent variations in electrophysiological and fMRI responses, which were characteristic for each stimulus protocol. Depending on the IPI, the magnitude of the fMRI response either correlated strongly with or was apparently unrelated to the spiking or postsynaptic activity of the granular cells. A strong relation between spiking activity and resultant fMRI response was only found when the stimulation protocol caused an increase in the recorded population spike latency. If the latency was decreased, the fMRI response was more closely related to the applied input activity. Perforant pathway fibers monosynaptically activate granular cells, so variations in population spike latencies reflect changes in their intrinsic excitability. Therefore, during increased intrinsic excitability, signaling cascades upstream of the granular cells determine the fMRI response, whereas granular cell activity-related mechanisms control the fMRI response during decreased intrinsic excitability.