Rapid eye movement sleep promotes fear conditioning-induced dendritic spine elimination of layer 2/3 pyramidal neurons in the mouse motor cortex

Abstract

Background: Previous studies have shown that rapid eye movement (REM) sleep is important for promoting dendritic spine elimination after fear learning as well as for selectively maintaining new dendritic spines after motor learning. These REM sleep-dependent synaptic changes were measured on apical dendrites of layer 5 pyramidal neurons. Whether and how REM sleep affects synaptic structural plasticity on other cell types in the cortex remain unclear.

Methods: Used transcranial two-photon microscopy, we examined the effects of auditory cued fear conditioning (FC) and REM sleep on changes of dendritic spines of layer 2/3 pyramidal neurons in the mouse primary motor cortex.

Results: Auditory cued FC induced significantly higher elimination and formation of dendritic spines of layer 2/3 pyramidal neurons in the primary motor cortex over 4 hours. The degree of spine elimination rate was correlated with the freezing response during the 24 hour-recall test. Notably, REM sleep deprivation after FC prevented dendritic spine elimination, but not formation, of layer 2/3 pyramidal neurons. Furthermore, Ca²⁺ activity of layer 2/3 pyramidal neurons significantly increased during REM sleep, and that optogenetic blockade of Ca²⁺-CaMKII signaling during REM sleep prevented FC-induced spine elimination.

Conclusion: These findings reveal an important role of REM sleep in FC-induced pruning of dendritic spines of layer 2/3 pyramidal neurons in the motor cortex.

Keywords

Ca²⁺activity / fear conditioning / motor cortex / REM sleep / synaptic dynamics

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