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

Dendritic spine dynamics of Layer 5 Pyramidal neurons (L5PNs) are thought to be physical substrates for motor learning and memory of motor skills and altered spine dynamics are frequently correlated with poor motor performance. Here we describe an exception to this rule by studying mice lacking Paired immunoglobulin receptor B (PirB-/-). Using chronic two-photon imaging of primary motor cortex (M1) of PirB-/-;Thy1-YFP-H mice, we found a significant increase in the survival of spines on apical dendritic tufts of L5PNs, as well as increased spine formation rates and spine density. Surprisingly and contrary to expectations, adult PirB-/- mice learn a skilled reaching task more rapidly compared to wild type (WT) littermate controls. Conditional excision of PirB from forebrain pyramidal neurons in adult mice replicated these results. Furthermore, chronic imaging of L5PN dendrites throughout the learning period revealed that the stabilization of learning-induced newly formed spines is significantly elevated in PirB-/- mice. The degree of survival of newly formed spines in M1 yielded the strongest correlation with task performance, suggesting that this increased spine stability is advantageous and can translate into enhanced acquisition and maintenance of motor skills. Notably, inhibiting PirB function acutely in M1 of adult WT mice throughout training increases the survival of spines formed during early training and enhances motor learning. These results suggest that increasing the stability of newly formed spines is sufficient to improve long-lasting learning and motor performance and demonstrate that there are limits on motor learning that can be lifted by manipulating PirB, even in adulthood.