Sleepless nights, vanishing faces: The effect of sleep deprivation on long-term social recognition memory in mice

Sleep deprivation (SD) detrimentally affects hippocampal-dependent memories, notably spatial and fear memories. However, its effect on social recognition memory — crucial for identifying conspecifics, remains unexplored. To address this, we developed a novel protocol to study the effects of SD on long-term social recognition memory (SRM) in adult male C57BL/6J mice. Our study revealed that 6 hours of SD, following a socialization trial, caused amnesia when SRM was assessed 24 hours later.
Next, we investigated whether SD causes permanent loss or suboptimal storage of SRM. We employed mouse models equipped for tagging and optogenetic reactivation of key hippocampal neuronal ensembles involved in memory storage and retrieval (i.e. memory engrams). We found that SRMs affected by SD were suboptimally stored, as demonstrated by successful optogenetic retrieval up to 6 days post-socialization.
These findings led us to investigate the mechanisms underlying the impairments using a clinically approved PDE4 inhibitor to elevate cAMP levels before testing. Our results showcased that SRMs formed under SD conditions could be successfully retrieved by pharmacological intervention, hinting at how SD might affect SRM retrieval via cAMP signalling. Moreover, by combining optogenetic and pharmacological strategies, we demonstrated the potential to persistently reverse SRM deficits several days after socialization, without any intervention immediately before testing. Our current efforts focus on understanding how SD affects the functional connectivity between memory engram cells.
Overall, our research provides valuable insights into adverse effects of SD on social functioning and may inform the development of novel interventions to promote optimal sleep and cognitive functioning.