Fear conditioning and extinction induce opposing dendritic spine plasticity in neocortex

Symposia 09: Synaptic and Network Plasticity in Development and LearningFear conditioning is an associative learning in which a conditioned neutral stimulus is paired with an aversive unconditioned stimulus to elicit fear response. Repeated exposures to conditioned stimulus diminish the expression of fear response, a process called extinction. Although it is generally believed that fear extinction is a form of new learning that inhibits rather than erases previously acquired fear memories, the hypothesis that extinction causes the partial erasure of fear memories remains viable. To investigate how neural circuits are modified by fear learning and extinction, we used transcranial two-photon microscopy to examine the formation and elimination of postsynaptic dendritic spines of layer V pyramidal neurons in mouse neocortex. We found that fear conditioning by pairing an auditory cue with a footshock increases the rate of spine elimination in mouse frontal association cortex. In contrast, fear extinction by repeated presentation of the same auditory cue without a footshock increases the rate of spine formation. Notably, spine elimination and formation induced by fear conditioning and extinction occur on the same dendritic branches in a cue- and location-specific manner. Furthermore, reconditioning preferentially induces elimination of dendritic spines that were formed after extinction. Thus, within vastly complex neuronal networks, fear conditioning, extinction and reconditioning lead to opposing changes at the level of individual synapses. We recently found that this opposing dendritic spine plasticity was also observed in auditory cortex. These findings suggest that fear memory trace erasure could be a universal phenomenon in neocortex after fear extinction