| A conditioned taste aversion (CTA) rapidly develops if initial exposure to a taste is followed by gastrointestinal illness. Novel tastes are readily associated with illness, while familiar tastes are not. To identify molecular signals that underlie novel taste effectiveness, immunostaining for c-fos protein was used to mark neurons that respond differentially to novel and familiar tastes. Novel tastes induced more robust fos-like immunoreactivity (FLI) in insular cortex (IC) and central amygdala than familiar tastes. The FLI expression showed a strong relationship with degree of taste familiarity, and displayed temporal dynamics suitable for long-delay learning. These results point to c-fos expression in IC and central amygdala as a key signaling event underlying taste processing during acquisition. Learning-specific patterns of neuronal activation can be similarly identified by varying taste novelty during conditioning. Novel taste-toxin pairing induced stronger FLI activation than familiar taste pairing. Widespread differential activation points to a learning circuit that engages brainstem, pontine, and forebrain structures. As IC is strongly implicated in taste processing, the effects of disrupting IC functioning on FLI expression to novel and familiar taste pairings were examined. Lesions of IC abolished FLI increases to novel pairing, suggesting a role in taste novelty detection, while reversible inactivation of IC during taste familiarization induced FLI increases to familiar pairing, implicating a role in taste memory formation. These findings support conclusions from behavioral studies, and suggest that c-fos may mediate the learning. cAMP-dependent protein kinase A (PKA) is involved in memory consolidation in other association learning paradigms. Using pharmacological and genetic approaches, we examined whether disruption of PKA interferes with CTA memory formation and consolidation. A selective PKA inhibitor infused intracerebroventricularly during conditioning weakened CTA memory as evident by rapid extinction. The same treatment directed at amygdala had no effect on short-term but impaired long-term memory. Moreover, mutant mice lacking a regulatory subunit of PKA (RIIbeta) showed impairment in long-term, but not short-term, CTA memory, and had impaired FLI response specifically in amygdala to illness-inducing toxin. Collectively, these findings suggest PKA signaling is important for long-term CTA memory consolidation, and amygdala may be one site important for this activity. |
