Ultrastructural effects of learning and post-learning sleep on the dorsal striatum

In cortex and hippocampus, electrophysiological, molecular, and/or ultrastructural evidence shows that sleep promotes the weakening of most synapses. In primary motor cortex, immediately after training in the complex wheel task, sleep-dependent weakening spares the synapses that potentiated during learning. Together, these results show that sleep can at the same time reduce the cost of synaptic activity and promote memory consolidation. Here we used serial block-face scanning electron microcopy to measure synapse number and size of the axon-spine interface (ASI), an ultrastructural measure of synaptic strength, in the medium size spiny neurons of the mouse dorsomedial (DM) and dorsolateral (DL) striatum. Previous work found that DM is involved in the early phase of motor learning, while DL is engaged later when the task becomes automatic. Four experimental groups were used: mice extensively trained in the complex wheel task for 1 hour (T), untrained awake controls (W), and mice allowed to sleep (S) or sleep deprived (SDep) for 6 hours immediately after training (4-5 male mice/group; at least 401 ASIs/mouse/region). In DM, ASI size increases immediately after skill training in large sets of spines with high plastic potential (with endosomes and without spine apparatus) and, several hours later, the overall number of synapses decreases after sleep but not after sleep deprivation. In DL, the post-training increase in ASI size is restricted to fewer spines and is not followed by sleep-dependent synaptic changes. Thus, post-learning synaptic pruning afforded by sleep may be especially important early in the training, before the task becomes automatic. Statement of Significance Sleep promotes the consolidation of motor memories in rodents and humans, but the underlying mechanisms are poorly characterized. In dorsomedial striatum, which is involved in the early phase of learning when movements are imprecise, we find that skill training leads, in most spines, to an increase in the axon-spine interface (ASI), an ultrastructural measure of synaptic strength, and post-learning sleep, but not post-learning sleep deprivation, decreases the number of excitatory synapses. In dorsolateral striatum, which is engaged when the task becomes automatic, the post-training increase in ASI size affects fewer spines and is not followed by sleep-dependent synaptic changes. Synaptic pruning during sleep may therefore be especially important during the early phase of consolidation of a motor skill.