Recent use of manganese-enhanced MRI (MEMRI) to assess the neural circuitry involved in autonomic and somatosensory paradigms has been promising. The current study addresses the feasibility of utilizing this technique to assess more complex cognitive and emotional processes. Since olfactory cues are particularly salient to animals, we utilized odorless air, novel/arousing and novel/fear-inducing scents to assess the neural circuitry sub-serving novelty and unconditioned fear. The present imaging data clearly indicate that animals with no prior exposure to a threat-inducing emotional stimulus selectively activated the unconditional fear neuronal pathway, specifically with heightened amygdala and hypothalamic activation. While animals exposed to the novel/arousing compared to fear-inducing odor demonstrated enhanced uptake in the cingulated and prefrontal cortices. In addition, as expected the hippocampus showed significantly enhanced manganese contrast after novelty exposure. Therefore the current study support the validity of MEMRI in the exploration of highly relevant complex neural circuitries associated with cognition and emotion.