Mapping cerebral blood flow changes during auditory-cued conditioned fear in the nontethered, nonrestrained rat.

Conditioned fear (CF) is one of the most frequently used behavioral paradigms; however, little work has mapped changes in cerebral perfusion during CF in the rat-the species which has dominated CF research. Adult rats carrying an implanted minipump were exposed to a tone (controls, n = 8) or a tone conditioned in association with footshocks (CS group, n = 9). During reexposure to the tone 24 h later, animals were injected intravenously by remote activation with [14C]-iodoantipyrine using the pump. Significant group differences in regional CBF-related tissue radioactivity (CBF-TR) were determined by region-of-interest analysis of brain autoradiographs, as well as in the reconstructed, three-dimensional brain by statistical parametric mapping (SPM). CS animals demonstrated significantly greater, fear-enhanced increases in CBF-TR in auditory cortex than controls. The lateral amygdala was activated, whereas the basolateral/basomedial and central amygdala were deactivated. In the hippocampus and medial prefrontal cortex, CBF-TR increased significantly ventrally but not dorsally. Significant activations were noted in medial striatum and the thalamic midline and intralaminar nuclei. However, the ventrolateral/dorsolateral striatum and its afferents from motor and somatosensory cortex were deactivated, consistent with the behavioral immobility seen during CF. Significant activations were also noted in the lateral septum, periaqueductal gray, and deep mesencephalic nucleus/tegmental tract. Our results show that auditory stimuli endowed with aversive properties through conditioning result in significant redistribution of cerebral perfusion. SPM is a useful tool in the brain mapping of complex rodent behaviors, in particular the changes in activation patterns in limbic, thalamic, motor, and cortical circuits during CF.