Frequency-dependent activation pattern in the rat hippocampus, a simultaneous electrophysiological and fMRI study

Frequency-dependent hippocampal activation during electrical perforant pathway stimulation was analyzed simultaneously by electrophysiological recordings in dentate gyrus and functional magnetic resonance imaging (fMRI). Pulse trains at low-frequency stimulation (2.5 Hz) did not influence electrophysiological responses within stimulation trains in the dentate gyrus and triggered no detectable BOLD responses. Increased stimulation frequencies (5.0-20 Hz) generated a roughly linear enhancement of the BOLD response. The BOLD signal within the dentate gyrus correlated more closely with stimulus pattern than with generated action potentials of the granular cells. However, the BOLD signal was strongly influenced by additional local signal processing activated by repetitive stimulus trains. fMRI visualized a frequency-specific spatial activation pattern of the hippocampus; spatially restricted activation in the dentate gyrus during 5-Hz stimulation, activation of the entire hippocampus and subiculum at 10 Hz and activation of the contralateral hippocampus during 20-Hz stimulation.