Genetic tracing of bitter taste-relaying neurons reveals a change in populations of the conditioned stimulus-activated neurons in the medial amygdala during conditioned taste aversion learning.

Genetic tracing revealed that subsets of neurons in the medial amygdala (MeA) were labeled with the transneuronal tracer tWGA-DsRed originating from bitter taste receptor cells in male mice, suggesting the locations of bitter taste-relaying neurons in the MeA. Although not many studies have reported the involvement of MeA neurons in taste information processing, several studies clearly indicated that the MeA neurons play an important role in taste neophobia that refers to a reduction in consumption of a novel taste. On the other hand, several amygdaloid nuclei of the amygdala also operate to acquire conditioned taste aversion (CTA), which taste novelty determines the efficiency and strength for, while processing the conditioned stimulus (CS) followed by the unconditioned one (US) to elicit behavioral aversion to the CS. Here we combined genetic tracing and immunohistochemical analyses to examine whether subpopulations of tWGA-DsRed-labeled MeA neurons which inherently receive aversive bitter input can induce changes in responses to the novelty of saccharin and the CS saccharin during CTA learning. Immunohistochemical detection of Zif268 induction revealed that saccharin activated more tWGA-DsRed-labeled MeA neurons of mice that experienced saccharin at the first time than it did in mice experiencing saccharin multiple times. The CS saccharin activated a larger number of tWGA-DsRed-labeled MeA neurons after mice acquired CTA memory, compared with those detected in mice without CTA. Our results also suggest that the increased population of the CS-activated neurons among tWGA-DsRed-labeled MeA neurons may remain unchanged and activated by the CS after the subsequent extinction of CTA memory.