Low frequency stimulation of the perforant pathway generates anesthesia-specific variations in neural activity and BOLD responses in the rat dentate gyrus.

To study how various anesthetics affect the relationship between stimulus frequency and generated functional magnetic resonance imaging (fMRI) signals in the rat dentate gyrus, the perforant pathway was electrically stimulated with repetitive low frequency (i.e., 0.625, 1.25, 2.5, 5, and 10 Hz) stimulation trains under isoflurane/N(2)O, isoflurane, medetomidine, and α-chloralose. During stimulation, the blood oxygen level-dependent signal intensity (BOLD response) and local field potentials in the dentate gyrus were simultaneously recorded to prove whether the present anesthetic controls the generation of a BOLD response via targeting general hemodynamic parameters, by affecting mechanisms of neurovascular coupling, or by disrupting local signal processing. Using this combined electrophysiological/fMRI approach, we found that the threshold frequency (i.e., the minimal frequency required to trigger significant BOLD responses), the optimal frequency (i.e., the frequency that elicit the strongest BOLD response), and the spatial distribution of generated BOLD responses are specific for each anesthetic used. Concurrent with anesthetic-dependent characteristics of the BOLD response, we found the pattern of stimulus-induced neuronal activity in the dentate gyrus is also specific for each anesthetic. Consequently, the anesthetic-specific influence on local signaling processes is the underlying cause for the observation that an identical stimulus elicits different BOLD responses under various anesthetics.