Enhancing motor learning by increasing the stability of newly formed dendritic spines in the motor cortex

Dendritic spine dynamics are thought to be substrates for motor learning and memory, and altered spine dynamics often lead to impaired performance. Here, we describe an exception to this rule by studying mice lacking paired immunoglobulin receptor B (PirB^-/-). Pyramidal neuron dendrites in PirB^-/- mice have increased spine formation rates and density. Surprisingly, PirB^-/- mice learn a skilled reaching task faster than wild-type (WT) littermates. Furthermore, stabilization of learning-induced spines is elevated in PirB^-/- mice. Mechanistically, single-spine uncaging experiments suggest that PirB is required for NMDA receptor (NMDAR)-dependent spine shrinkage. The degree of survival of newly formed spines correlates with performance, suggesting that increased spine stability is advantageous for learning. Acute inhibition of PirB function in M1 of adult WT mice increases the survival of learning-induced spines and enhances motor learning. These results demonstrate that there are limits on motor learning that can be lifted by manipulating PirB, even in adulthood.