The application of functional magnetic resonance imaging (fMRI) to visualize brain regions involved in emotion has considerably improved our understanding of human neurobiology. Progress has been much slower in applying this approach to conscious animals, due to obstacles such as immobility in the magnet and ability to perform tasks within a dark, narrow, horizontal space. These obstacles have been overcome with the recent invention of a small animal holding device for performing fMRI on fully awake rodents ranging in weight from 300 - 500g. Since fMRI research paradigms can now be performed in animals without injury or sacrifice, they provide new research opportunities for studies in areas where multiple time points in brain functioning can be assessed non-invasively, thereby allowing spatial as well as temporal mapping. This proposal describes a novel approach for mapping the fear response in the anaesthetized rat with fMRI. These studies will use fMRI to identify and monitor neuronal activation associated with fearfulness. For most animals, a primary fear-eliciting event is the possibility of being attacked by a predator. Consequently, predator stress is currently being simulated under laboratory conditions to trigger unconditioned (innate) fear responses in animals. Recent reports suggest that changes in neuroendocrine status of an animal may be central to fear response. In addition, drug intervention strategies have pointed to the inherent plasticity of the neural systems underlying this emotion. To test the hypothesis that unconditioned fear triggered by the scent of a predator will result in alterations in neuronal activation in a manner that reflect the neuroendocrine status and pharmacological response of an animal, we will utilize the technological advances for performing fMRI non-invasively in a conscious animal. The long-term goal of this research is to provide an understanding of the unique features of central mechanisms that regulate fearfulness and the impact of the neuroendocrine and neuropharmacological status on the processing of this emotion. Since fear experience by all animals, these studies may expand our understanding of anxiety and phobias in general.
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