Investigating the synaptic dynamics of adaptive behavior in the mouse frontal cortex

In this world of unexpected change, animals face a critical trade-off between retaining older information and facilitating new learning. Dendritic spines, where excitatory synapses are located, represent the basic structural and functional unit of learning and memory at the neuronal level; spines are formed and/or modified during learning to support behavioral demands. However, how the interplay between plasticity and stability in dendritic spines is implemented to accommodate adaptations in behavior remains unclear. We investigated this question in head-fixed mice performing a rule-switch behavioral task. We found that the secondary motor cortex (M2) of the dorsal prefrontal cortex (dPFC) is essential for changing strategy in response to external stimuli, but not for the maintenance of a strategy. Bilateral inactivation of M2 impaired the switch to the new rule by increasing the perseverative errors. Moreover, in-vivo imaging of spines in M2 pyramidal neurons across behavioral sessions after the rule switch, revealed an increase in spine dynamics (spine turnover) that was significantly higher in mice learning to adapt compared to mice maintaining a previously learned strategy. These results uncover an important role of M2 persistent synaptic changes in adaptive behavior.