Conclusion

Our study provides the first evidence of age-dependent effects of ASIC1A on Pavlovian fear conditioning and provides the first evidence that its effects on cued and contextual fear conditioning are separable. It is remarkable that effects of ASIC1A deficiency on cue-evoked fear memory recall emerge in a timeframe that comprises the late preweaning period (P18) and the early postweaning period (P23). This is the time when the appropriate assessment of threats becomes vital. Context-evoked fear memory, however, is largely impaired in Asic1a_-/-_ mice of all ages. Asic1a_-/-_ mice trained at P17 do not robustly acquire contextual fear memory, but Asic1a_-/-_ mice trained at older ages acquire context memory, suggesting a delayed circuit development in those mice. Notably, the stability of context-evoked fear memory over time is achieved at older ages than stability of cue-evoked fear memory, also suggesting a delayed development of the circuits relevant for contextual fear memory.

Overall, our results suggest a complex role of ASIC1A in the maturation and/or function of circuits relevant to Pavlovian fear conditioning.