Abstract
Mounting evidence suggests that neural oscillations are related to the learning and consolidation of newly formed memory in the mammalian brain. Four to seven Hertz (4-7 Hz) oscillations in the prefrontal cortex are also postulated to be involved in learning and attention processes. Additionally, slow delta oscillations (1-4 Hz) have been proposed to be involved in memory consolidation or even synaptic down scaling during sleep. The molecular mechanisms which link learning-related oscillations during wakefulness to sleep-related oscillations remain unknown. We show that increasing the expression of calcium/calmodulin dependent protein kinase IV (CaMKIV), a key nucleic protein kinase, selectively enhances 4-7.5 Hz oscillation power during trace fear learning and slow delta oscillations during subsequent sleep. These oscillations were found to be boosted in response to the trace fear paradigm and are likely to be localized to regions of the prefrontal cortex. Correlation analyses demonstrate that a proportion of the variance in 4-7.5 Hz oscillations, during fear conditioning, could account for some degree of learning and subsequent memory formation, while changes in slow delta power did not share this predictive strength. Our data emphasize the role of CaMKIV in controlling learning and sleep-related oscillations and suggest that oscillatory activity during wakefulness may be a relevant predictor of subsequent memory consolidation.
Highlights
There is evidence that these prefrontal 4-7.5 Hz rhythms, which exist in mice, rats, monkeys and humans, are involved in attention and learning processes [1,2,3,4]
The frequency of occurrence of each particular sleep-wake state during the light (F(1,6) = 0.016, p = 0.904, two-way ANOVA) and dark period (F(1,6) = 0.001, p = 0.975, two-way ANOVA) was not different between wild type (WT) and calmodulin dependent protein kinase IV (CaMKIV) over-expressed mice (Table 1). These results show that CaMKIV over-expression augments delta-related EEG oscillations in the sleep recording environment without impacting the time spent sleeping or the frequency of sleep
We show that accentuation of trace fear learning, through reduction of the trace fear interval, produces increases in oscillation power during both learning and subsequent sleep
Summary
There is evidence that these prefrontal 4-7.5 Hz rhythms, which exist in mice, rats, monkeys and humans, are involved in attention and learning processes [1,2,3,4]. Human and rodent studies suggest that slow oscillations during sleep are related to memory [5,6,7,8]. Parallel studies examining single neuron recording in the prefrontal and hippocampal cortex show that there is a network of information replay during sleep, which reflects learning during the days experience [9,10,11,12]. There is evidence for neural replay in the hippocampus during periods of wakefulness [13,14].
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