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Prolonged wakefulness enhances motor skill consolidation through dopamine D1 receptor-expressing neurons in the dorsomedial striatum in mice

Lu Wang  Wan-kun Gong  Jian Ni  Zhi-li Huang  
【摘要】:Introduction It is widely acknowledged that sleep is essential for memory consolidation. However, for procedural memory that is dependent on the striatum, the effect of sleep on memory consolidation is equivocal, and the underlying cellular and molecular mechanisms remain largely unknown. In this study, we aimed to explore the cellular and molecular substrates underlying sleep-related motor skill consolidation in the mouse striatum. Materials and methods Adult C57 BL6/J, Drd1-Cre, or Drd2-eGFP male mice with sleep deprivation(SD) for 6 h on a slowly moving treadmill and with undisturbed sleep(non-SD) were used. In the dorsomedial striatum(DMS) as well as the dorsolateral striatum(DLS) of mice, the number of dendritic spines was examined by Golgi staining, and the AMPA receptor mediated miniature excitatory postsynaptic currents(mEPSCs) were recorded by whole-cell patch-clamp recordings. Furthermore, the c-fos expression was examined by immunohistochemistry, and the motor skill consolidation was assessed by the accelerating rotarod task. Results SD for 6 h caused a significant increase in the number of spine density and the amplitude of mEPSCs in the DMS but not in the DLS. Surprisingly, SD after learning enhanced motor skill consolidation in the rotarod task. In addition, the expression of c-fos was significantly elevated in dopamine D1 receptor-expressing(D1R) neurons in the DMS in SD compared with non-SD mice. Chemogenetic inhibition of D1R neurons or pharmacologically blocking D1 or NMDA receptors in the DMS prevented SD-induced enhancement of motor skill consolidation. Conclusion Brief SD enhances motor skill consolidation, possibly through potentiating the synaptic plasticity and increasing the activity of D1R neurons in the DMS, suggesting that prolonged wakefulness after learning is essential for the consolidation of motor memory traces.

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