Disruption of NREM sleep and sleep-related spatial memory consolidation in mice lacking adult hippocampal neurogenesis

Abstract

Cellular plasticity at the structural level and sleep at the behavioural level are both essential for memory formation. The link between the two is not well understood. A functional connection between adult neurogenesis and hippocampus-dependent memory consolidation during NREM sleep has been hypothesized but not experimentally shown. Here, we present evidence that during a three-day learning session in the Morris water maze task a genetic knockout model of adult neurogenesis (Cyclin D2−/−) showed changes in sleep macro- and microstructure. Sleep EEG analyses revealed a lower total sleep time and NREM fraction in Cyclin D2−/− mice as well as an impairment of sleep specific neuronal oscillations that are associated with memory consolidation. Better performance in the memory task was associated with specific sleep parameters in wild-type, but not in Cyclin D2−/− mice. In wild-type animals the number of proliferating cells correlated with the amount of NREM sleep. The lack of adult neurogenesis led to changes in sleep architecture and oscillations that represent the dialog between hippocampus and neocortex during sleep. We suggest that adult neurogenesis—as a key event of hippocampal plasticity—might play an important role for sleep-dependent memory consolidation and modulates learning-induced changes of sleep macro- and microstructure.

Effects of Alcohol Withdrawal on Sleep Macroarchitecture and Microarchitecture in Female and Male Rats

“…During acute alcohol withdrawal, despite no overall change in spindle duration, there was an increase in intra-spindle frequency (i.e., the rate of spindle oscillation) that returned to baseline levels during protracted abstinence. Sleep spindles are considered to be sleep-protective elements, shielding NREM sleep from spontaneous sensory input or disruptions, possibly at the expense of REM sleep (Fernandez and Lüthi, 2020;Sippel et al, 2020). Thus, the lack of change in the time spent in NREM sleep and the decreased time in REM sleep found in the current study may reflect the influence of NREM sleep spindles during acute withdrawal from alcohol.…”

Adult-born neurons add flexibility to hippocampal memories

“…abGCs active during CFC learning are reactivated during rapid eye movement (REM) sleep, and both optogenetic stimulation and silencing of reactivated abGCs disrupt consolidation ( Kumar et al, 2020 ). Blocking neurogenesis reduces non-REM sleep and disrupts consolidation-related oscillations and cortex-hippocampus interaction, leading to poor spatial memory performance ( Sippel et al, 2020 ). Further, the rate of neurogenesis also seems to determine the hippocampus-dependent period of memories ( Kitamura et al, 2009 ).…”

Adult Neurogenesis under Control of the Circadian System

“…This scarce activity is essential for REM sleep-dependent memory consolidation [ 137 , 138 ], indicating that sleep is essential for newborn neuron functionality. Interestingly, mice lacking adult neurogenesis reveal shorter sleep time due to NREM sleep disruption and higher sleep fragmentation [ 139 ], suggesting a bidirectional interaction between sleep and adult neurogenesis. Importantly, exogenous administration of melatonin, inducing alignment of circadian rhythms [reviewed by [ 140 ]], increases NPC proliferation in sleep-deprived mice and provides a neuroprotective effect against the deleterious effects of REM sleep deprivation [ 141 ].…”