No abstract

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.

To evaluate functional neuronal compensation after partial damage to the nigrostriatal system, we lesioned rats unilaterally in the striatum with 6-hydroxydopamine. Five weeks later, cerebral perfusion was mapped at rest or during treadmill walking using [(14)C]-iodoantipyrine. Regional CBF-related tissue radioactivity (CBF-TR) was quantified by autoradiography and analyzed by statistical parametric mapping and region-of- interest analysis. Lesions were confirmed by tyrosine hydroxylase immunohistochemistry and changes in rotational locomotor activity. Functional compensations were bilateral and differed at rest and during treadmill walking. Consistent with the classic view of striatopallidal connections, CBF-TR of lesioned compared to sham-lesioned rats increased in the ipsilateral subthalamic nucleus (STN) and internal globus pallidus, and decreased in the striatum and external globus pallidus. Contrary to the classic view, CBF-TR increased in the ipsilateral ventral lateral, ventral anterior thalamus and motor cortex, as well as in the central medial thalamus, midline cerebellum, and contralateral STN. During walking, perfusion decreased in lesioned compared to sham-lesioned rats across the ipsilateral striato-pallidal-thalamic-cortical motor circuit. Compensatory increases were seen bilaterally in the ventromedial thalamus and red nucleus, in the contralateral STN, anterior substantia nigra, subiculum, motor cortex, and in midline cerebellum. Enhanced recruitment of associative sensory areas was noted cortically and subcortically. Future models of compensatory changes after nigrostriatal damage need to address the effects of increased neural activity by residual dopaminergic neurons, interhemispheric interactions and differences between resting and locomotor states. Identification of sites at which functional compensation occurs may define useful future targets for neurorehabilitative or neurorestorative interventions in Parkinson's disease.