Role of densin-180 in mouse ventral hippocampal neurons in 24-hr retention of contextual fear conditioning

Introduction: Densin-180 interacts with postsynaptic molecules including calcium/calmodulin-dependent protein kinase II alpha (CaMKII alpha) but its function in learning and memory process has been unclear. Methods: To investigate a role of hippocampal densin-180 in contextual fear conditioning (CFC) learning and memory processes, knockdown (KD) of densin-180 in hippocampal subareas was applied. Results: First, ventral hippocampal (vHC) densin-180 KD impaired single-trial CFC (stCFC) memory one day later. stCFC caused freezing behaviors to reach the peak about one hour later in both control and KD mice, but then freezing was disappeared at 2 hr postshock in KD mice. Second, stCFC caused an immediate and transient reduction of vHC densin-180 in control mice, which was not observed in KD mice. Third, stCFC caused phosphorylated-T286 (p-T286) CaMKII alpha to change similarly to densin-180, but p-T305 CaMKII alpha was increased 1 hr later in control mice. In KD mice, these effects were gone. Moreover, both basal levels of p-T286 and p-T305 CaMKII alpha were reduced without change in total CaMKII alpha in KD mice. Fourth, we found double-trial CFC (dtCFC) memory acquisition and retrieval kinetics were different from those of stCFC in vHC KD mice. In addition, densin-180 in dorsal hippocampal area appeared to play its unique role during the very early retrieval period of both CFC memories. Conclusion: This study shows that vHC densin-180 is necessary for stCFC memory formation and retrieval and suggests that both densin-180 and p-T305 CaMKII alpha at 1 similar to 2 hr postshock are important for stCFC memory formation. We conclude that roles of hippocampal neuronal densin-180 in CFC are temporally dynamic and differential depending on the pattern of conditioning stimuli and its location along the dorsoventral axis of hippocampal formation.