Effects of intra-hippocampal corticosterone and sleep on consolidation of complex memory of aversive experience in rats

Abstract

Formation and consolidation of memories for highly stressful (traumatic) events is a complex process that involves interplay between multiple memory systems and has implications for etiology and treatment of stress- and trauma-related disorders. Here we study effects of sleep/wake state and high intra-hippocampal corticosterone on consolidation of aversive contextual memories as well as consolidation of association between simple trauma-related cues and fear response in rats. Animals were implanted with EEG and EMG electrodes for sleep assessment and cannulas for intra-hippocampal corticosterone application. They were familiarized to a "safe box" and then trained in fear conditioning paradigm in a distinct "shock box" with a prominent simple auditory cue serving as a phasic background cue. Immediately after conditioning, animals received bilateral intra-hippocampal saline (1l) or corticosterone (10ng in 1l saline) injection and were either allowed to sleep or were kept awake for a following two-hour consolidation period. Memory test twenty-four hours later revealed that the saline-injected animals with sleep during consolidation had significantly stronger freezing response in the shock box compared to the safe box as well as increased freezing in response to the tone. Lack of post-learning sleep in saline injected animals led to generalization of fear response to the safe context, while association between simple cue and fear response was preserved. High intra-hippocampal corticosterone level during memory consolidation led to generalization of fear response to the safe context, regardless of sleep/wake state, while enhancement of response to single stimulus was not observed. Our results show how manipulation of conditions during consolidation can lead to greatly variable complex memories for a traumatic episode and distinct behavioral outcomes. HighlightsO_LIWe studied effect of sleep and intrahippocampal corticosterone on consolidation of memories surrounding stressful event modeled by fear conditioning in rats. C_LIO_LISleep following traumatic fear conditioning event is important for subsequent manifestation of fear response (freezing) specifically in the context of traumatic event but not in a neutral safe context. C_LIO_LILack of sleep or high intra-hippocampal corticosterone level during memory consolidation leads to generalization of fear response to both the traumatic and safe context. C_LIO_LIIncreased freezing in response to a trauma-related auditory cue was observed in saline injected rats regardless of wake/sleep state during consolidation. C_LIO_LIPost-learning intra-hippocampal corticosterone injection blocked response to a trauma-related auditory cue regardless of wake/sleep state during consolidation. C_LI