Functional neuroimaging of aversive taste-related areas in the alert rat revealed by positron emission tomography

Among noninvasive functional brain imaging techniques, ¹⁸F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) has a comparative advantage in detecting active brain regions in freely locomoting animals. We developed an [¹⁸F]FDG-PET protocol that visualizes active brain regions that respond preferentially to citrate-induced multiple behaviors in freely locomoting rats. In addition, c-Fos immunohistochemistry, an activity-dependent mapping, was performed to examine whether the areas detected by PET correspond to regions with c-Fos-immunopositive neurons. Citrate (0.1 M) was intraorally applied to detect activated brain regions responding to gustation and the rejection behaviors including gaping and tongue protrusion, which would potently activate the limbic system. PET images during citrate stimulation were subtracted from those obtained during free locomotion or during application of distilled water. Citrate increased FDG signals in multiple gustation-related regions: the nucleus accumbens (core and shell), the ventromedial nucleus of the thalamus, the basolateral and central nuclei of the amygdala, the hypothalamus, and the insular cortex. In addition, the ventrolateral striatum and the cingulate and entorhinal cortices, which have received less attention in the field of gustatory studies, also showed an increase in FDG signals. As expected, c-Fos-immunopositive cells were also found in these regions, suggesting that increased FDG signals induced by intraoral citrate injection are likely to reflect neural activity in these regions. Our [¹⁸F]FDG-PET protocol reveals the contributions of multiple brain regions responding to aversive taste in freely locomoting rats, and this approach may aid in the identification of unknown neural networks especially relating to the limbic information processing.