Functional mapping of rat barrel activation following whisker stimulation using activity-induced manganese-dependent contrast

Background: Cortical whisker barrels in the primary somatosensory cortex are a well-known example of brain function in rodents. The well-defined relationship between barrels and whiskers makes this system a unique model to study neuronal function and plasticity. In this study, we sought to establish a feasible working protocol of applying manganese-enhanced MRI (MEMRI) to map the cortical barrels following whisker stimulation. Methods: The protocol was based on the principle of activity-induced manganese-dependent (AIM) contrast. Rats were prepared by sodium pentobarbital anesthetization, intraperitoneal manganese-chloride injection, right common carotid mannitol injection and temperature maintenance. Left whiskers were connected to a speaker through a cotton thread and were stimulated by a series of rectangular pulses. MEMRI was acquired with a 3T scanner 3 h after whisker stimulation. Before MR scanning, Wistar rats were euthanized to avoid motion artifacts. To improve the signal-to-noise ratio (SNR) and detection sensitivity, image coregistration, pixel intensity normalization, statistical mapping, group averaging and subtraction were performed. The AIM enhancement of the cortical barrels was quantified using volume of interest analysis on the acquired T1WI and R1 mapping. Results: Both experimental and control groups showed greater enhancement in the right hemisphere, same side as mannitol injection. In the experimental group, however, activity-induced enhancement was more localized in the right barrel fields, whereas in the control group, the enhancement was uniform throughout the right cortex. In the right cortical barrels, the enhancement ratios and R1 values in the experimental group were significantly higher than those in the control group. In the left cortical barrels, there was no significant difference between the two groups. Subtracted images and voxel-based statistical t-value mapping between experimental and control groups showed additional enhancement concentrated in the right cortical barrels. Conclusions: We have mapped rat whisker barrels using the AIM method and have shown a clear relationship between manganese-enhanced cortical regions and whisker tactile-sense-evoked activity. It is possible that, with sufficient SNR, the AIM method may reach whisker barrel discrimination, potentially useful to study plasticity in surgically or genetically manipulated rat brains.