Scientific Understanding of Consciousness
Dendritic Spine Remodelling
Nature, 483, 87–91, 1 March 2012
Opposite effects of fear conditioning and extinction on dendritic spine remodelling
Cora Sau Wan Lai, Thomas F. Franke & Wen-Biao Gan
Departments of Psychiatry and Pharmacology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA
It is generally believed that fear extinction is a form of new learning that inhibits rather than erases previously acquired fear memories. Although this view has gained much support from behavioural and electrophysiological studies, the hypothesis that extinction causes the partial erasure of fear memories remains viable. Using transcranial two-photon microscopy, we investigated how neural circuits are modified by fear learning and extinction by examining the formation and elimination of postsynaptic dendritic spines of layer-V pyramidal neurons in the mouse frontal association cortex. Here we show that fear conditioning by pairing an auditory cue with a footshock increases the rate of spine elimination. By contrast, fear extinction by repeated presentation of the same auditory cue without a footshock increases the rate of spine formation. The degrees of spine remodelling induced by fear conditioning and extinction strongly correlate with the expression and extinction of conditioned fear responses, respectively. Notably, spine elimination and formation induced by fear conditioning and extinction occur on the same dendritic branches in a cue- and location-specific manner: cue-specific extinction causes formation of dendritic spines within a distance of two micrometres from spines that were eliminated after fear conditioning. 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. These findings also suggest that fear memory traces are partially erased after extinction.
Classical fear conditioning is widely used to study associative learning in which a conditioned neutral stimulus (CS; for example an auditory cue) is paired with the presentation of an unconditioned aversive stimulus (US; for example a footshock) to elicit a conditioned response (CR; for example a freezing response to CS in the absence of US). Repeated exposures to CS diminish the expression of the CR, a process called extinction.
It is well accepted that synaptic reorganization is critical for learning and memory. However, it is unclear how synaptic circuits are modified by opposing forms of learning and how such modifications contribute to opposite behavioural outcomes. Our studies indicate that fear conditioning, extinction and reconditioning cause opposing synaptic modifications on the same dendritic branches in a cue- and location-specific manner. These findings also suggest that extinction induces at least partial erasure of fear memory traces, which have reciprocal connections with multiple brain areas including the amygdala, and its inactivation impairs fear learning and extinction suggesting that this region is directly involved in modulating behaviours.
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