The BOLD response in the rat hippocampus depends rather on local processing of signals than on the input or output activity. A combined functional MRI and electrophysiological study.

Functional magnetic resonance imaging (fMRI) of the human brain is widely used in neuroscience, but the exact relationship between measured fMRI response and the underlying changes in neuronal activity is still elusive. To obtain further information about the specific roles of synaptic (input) and spiking activity (output) for the generation of fMRI-related signals, we used an approach that combines electrophysiological and MRI measurements in the anatomically and physiologically well defined rat hippocampus. Direct electrical stimulation of the perforant pathway enabled us to control synchronized input activity to the dentate gyrus, whereas recorded population spikes from the granular cell layer indicated the dentate output activity. The perforant pathway was first stimulated with 15 identical pulse trains (10 Hz for 8 s), and evoked blood oxygenation level-dependent (BOLD) responses and population spikes were measured for each individual stimulus train. Spatial and magnitude aspects of the elicited BOLD responses differentially changed in the dentate gyrus and hippocampus from early to late stimulus trains together with population spike latencies in the dentate indicating delayed inhibitory network processing. Furthermore, the same number of stimuli presented in different patterns within trains (i.e., bursts of 10 stimuli at 50, 100, or 200 Hz) clearly altered the BOLD responses. Similarly, variations in the BOLD response also occurred when different stimulus patterns were chosen that caused the same number of population spikes. The results indicate that neuronal network activity including inhibitory interneurons rather than exclusively the input or spiking activity of the principal neurons determine a BOLD response to repetitive stimuli.

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.