Encoding of Discriminative Fear Memory by Input-Specific LTP in the Amygdala

• Published in: Neuron (Cambridge, Mass.) Vol. 95; no. 5; pp. 1129 - 1146.e5
• Main Authors: Kim, Woong Bin, Cho, Jun-Hyeong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.08.2017; Elsevier Limited
• Subjects: Acoustic Stimulation; Amygdala; Amygdala - physiology; Animals; Auditory Pathways - physiology; Conditioning (Psychology) - physiology; depotentiation; Discrimination (Psychology) - physiology; Electric Stimulation; electrophysiology; engram; Extinction, Psychological - physiology; Fear - physiology; fear conditioning; fear extinction; Female; Labeling; learning and memory; Long-term potentiation; Long-Term Potentiation - physiology; Long-Term Synaptic Depression - physiology; Male; Memory; Memory - physiology; Mice; Mice, Transgenic; neuromodulation; Neurons; optogenetics; Rodents; Synapses; neuromodulation; amygdala; fear conditioning; learning and memory; electrophysiology; fear extinction; optogenetics; engram; depotentiation; long-term potentiation
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2017.08.004

In auditory fear conditioning, experimental subjects learn to associate an auditory conditioned stimulus (CS) with an aversive unconditioned stimulus. With sufficient training, animals fear conditioned to an auditory CS show fear response to the CS, but not to irrelevant auditory stimuli. Although long-term potentiation (LTP) in the lateral amygdala (LA) plays an essential role in auditory fear conditioning, it is unknown whether LTP is induced selectively in the neural pathways conveying specific CS information to the LA in discriminative fear learning. Here, we show that postsynaptically expressed LTP is induced selectively in the CS-specific auditory pathways to the LA in a mouse model of auditory discriminative fear conditioning. Moreover, optogenetically induced depotentiation of the CS-specific auditory pathways to the LA suppressed conditioned fear responses to the CS. Our results suggest that input-specific LTP in the LA contributes to fear memory specificity, enabling adaptive fear responses only to the relevant sensory cue. [Display omitted] •LTP is not induced globally in ACx/MGN-LA pathways in discriminative fear learning•LTP is induced in CS+, but not CS–, pathways to LA in discriminative fear learning•Synapses in CS+ pathways to LA remain potentiated after fear extinction•Depotentiation of CS+, but not CS–, pathways to LA prevents the recall of fear memory Kim and Cho demonstrate that the formation of fear memory associated with a specific auditory cue requires selective synaptic strengthening in functionally defined neural pathways that convey the auditory signals to the amygdala.