Intravital imaging of dendritic spines in learning and memory

Dendritic spines are small protrusions extending from dendritic shafts of pyramidal neurons, which receive the vast majority of excitatory inputs in the brain. Majority of excitatory synapses in the central nervous system are located in dendritic spines, hence dendritic spines play a very important role in regulating neuronal excitability. Accumulating evidences have shown that substantial changes of dendritic spine have been correlated with animal behavior in different types of learning and leave long-lasting traces in the nervous system. By using in vivo transcranial two-photon imaging approach, we are able to image dendritic spine plasticity in the mouse neocortex. We used fear conditioning and fear extinction as two opposite learning paradigms to investigate how fear learning and unlearning affect the dendritic spine plasticity in the frontal association cortex. We found that auditory-cued fear conditioning induced dendritic spine elimination in the mouse frontal association cortex. In contrast, fear extinction increased dendritic spine formation in this region. We showed that dendritic spine elimination and formation induced by fear conditioning and extinction occurred on the same dendrites in a location- and cue-specific manner. These findings showed that within vastly complex neuronal networks, fear conditioning and extinction lead to opposing changes at the level of individual synapses in the frontal association cortex. In addition, our preliminary data showed that auditory-cued fear conditioning induced dendritic spine formation in the auditory cortex indicating that different cortical regions may response differently to the same learning task