Frequency-dependent neural activity, CBF, and BOLD fMRI to somatosensory stimuli in isoflurane-anesthetized rats

Inhalation anesthetics (e g isoflurane) are preferable for longitudinal fMRI experiments in the same animals. We previously implemented isoflurane anesthesia for rodent forepaw stimulation studies, and optimized the stimulus parameters with short stimuli (1-3-s long stimulation with ten electric pulses). These parameters, however, may not be applicable for long periods of stimulation because repetitive stimuli induce neural adaptation. Here we evaluated frequency-dependent responses (pulse width of 1 0 ms and current of 1.5 mA) for 30-s long stimulation under 1.3-1.5% isoflurane anesthesia. The cerebral blood flow (CBF) response (using laser Doppler flowmetry CBF(LDF)) and field potential (FP) changes were simultaneously measured for nine stimulus frequencies (1-24 Hz). CBF (using arterial spin labeling CBF(ASL)) and blood oxygenation level dependent (BOLD) fMRI responses were measured at 9.4 T for four stimulus frequencies (1 5-12 Hz) Higher stimulus frequencies (12-24 Hz) produced a larger FP per unit time initially, but decreased more rapidly later due to neural adaptation effects On the other hand, lower stimulus frequencies (1-3 Hz) induced smaller, but sustained FP activities over the entire stimulus period Similar frequency-dependencies were observed in CBF(LDF). CBF(ASL) and BOLD responses. A linear relationship between FP and CBF(LDF) was observed for all stimulus frequencies Stimulation frequency for the maximal cumulative neural and hemodynamic changes is dependent on stimulus duration, 8-12 Hz for short stimulus durations (<10 s) and 6-8 Hz for 30-s stimulation Our findings suggest that neural adaptation should be considered in determining the somatosensory stimulation frequency and duration under isoflurane anesthesia (C) 2010 Elsevier Inc All rights reserved