ストレス応答を増幅する記憶メカニズムの解析

抄録

Stress experiences induce diverse psychiatric symptoms. While stress experiences themselves are terminated within short time periods at a time scale of seconds or minutes, the stress-induced mood changes subsequently last for days or even a lifetime. This fact means that physiological activity not only during onsite stress episodes but also during post-stress periods may be crucial to facilitate stress-induced psychiatric changes. We hypothesized that this effect is mediated by memory processing mechanisms in the brain. A well-established theory of memory suggests that learned memory traces need to be consolidated into neuronal circuits for a long-term memory storage. Especially, the ventral part of the HC (vHC) is especially considered a crucial brain region for emotion- and sociality-related information processing and for memory consolidation. We tested this idea, mice were subjected to social defeat (SD) stress. Defeated mice showed deficits in social interactions. This reduction was suppressed by vHC inactivation, suggesting that vHC neuronal activity after stress experiences is especially crucial to induce social behavior deficit. To further examine detailed hippocampal activity patterns, we recorded spike patterns of vHC CA1 neurons using tetrode assemblies. Stress-encoding neurons in the vHC were continuously reactivated for several hours after SD experiences, which likely underlies the long-lasting effects of SD stress on social behavior. To further examine the causal of vHC activity in stress-induced behavioral changes, closed-loop feedback stimulation was applied to the vHC when synchronized reactivations of neuronal population in the vHC were detected. This manipulation abolished the stress-induced reductions in social interaction deficits, suggesting the importance of synchronized reactivation of vHC neurons for subsequent psychiatric responses. The vHC-specific activity patterns may serve as a biomarker and a therapeutic target in stress-induced mood disorders.