Reversing Pavlov: Memories of fearful associations, such as hearing a tone before receiving a low-voltage shock, are labile when they are retrieved, such that the association can be extinguished or reconsolidated. Monfils et al. (p. 951 , published online 2 April) demonstrate that applying a standard extinction treatment (sounding the tone multiple times in the absence of any shocks) within a window of time during which reconsolidation would normally occur has the effect of overwriting the original memory. Rats treated in this fashion display much lower levels of renewal (fear induced by sounding the tone once by itself), reinstatement (fear induced by giving the shock once by itself), and spontaneous recovery.

Humans and animals can learn that specific sensory cues in the environment predict aversive events through a form of associative learning termed fear conditioning. This learning occurs when the sensory cues are paired with an aversive event occuring in close temporal proximity. Activation of lateral amygdala (LA) pyramidal neurons by aversive stimuli is thought to drive the formation of these associative fear memories; yet, there have been no direct tests of this hypothesis. Here we demonstrate that viral-targeted, tissue-specific expression of the light-activated channelrhodopsin (ChR2) in LA pyramidal cells permitted optical control of LA neuronal activity. Using this approach we then paired an auditory sensory cue with optical stimulation of LA pyramidal neurons instead of an aversive stimulus. Subsequently presentation of the tone alone produced behavioral fear responses. These results demonstrate in vivo optogenetic control of LA neurons and provide compelling support for the idea that fear learning is instructed by aversive stimulus-induced activation of LA pyramidal cells.

Significance: An advantage of targeting reconsolidation to control reactions to learned threats is that the memory appears to be persistently altered, not inhibited. When these memories are diminished through extinction, the amygdala’s representation remains largely intact and the prefrontal cortex inhibits its expression, thus allowing the learned responses to recover. Targeting reconsolidation, therefore, should eliminate the necessity of prefrontal inhibition. We tested this hypothesis by contrasting standard extinction with extinction occurring during reconsolidation. We observed that behavioral interference of reconsolidation appears to bypass the prefrontal circuitry of extinction, inducing a more persistent loss of learned responses. Application of this strategy, which targets underlying learned threat processes, to fear and anxiety disorders may provide a more effective approach to treatment.

Motor skill acquisition occurs through modification and organization of muscle synergies into effective movement sequences. The learning process is reflected neurophysiologically as a reorganization of movement representations within the primary motor cortex, suggesting that the motor map is a motor engram. However, the specific neural mechanisms underlying map plasticity are unknown. Here the authors review evidence that 1) motor map topography reflects the capacity for skilled movement, 2) motor skill learning induces reorganization of motor maps in a manner that reflects the kinematics of acquired skilled movement, 3) map plasticity is supported by a reorganization of cortical microcircuitry involving changes in synaptic efficacy, and 4) motor map integrity and topography are influenced by various neurochemical signals that coordinate changes in cortical circuitry to encode motor experience. Finally, the role of motor map plasticity in recovery of motor function after brain damage is discussed.