Optical activation of lateral amygdala pyramidal cells instructs associative fear learning

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 28; pp. 12692 - 12697
• Main Authors: Johansen, Joshua P., Hamanaka, Hiroki, Monfils, Marie H., Behnia, Rudy, Deisseroth, Karl, Blair, Hugh T., LeDoux, Joseph E., McEwen, Bruce S.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 13-07-2010; National Acad Sciences
• Subjects: Amygdala; Amygdala - cytology; Amygdala - physiology; Animals; Associative learning; Behavioral neuroscience; Biological Sciences; Cells; Conditioning (Psychology) - physiology; Conditioning, Classical - physiology; Cues; Fear - physiology; Fear conditioning; Freezing; Genetics; Information processing; Lasers; Learning; Male; Memory; Mental stimulation; Neurons; Neurons - cytology; Neurons - physiology; Optics; Phobic Disorders; Photic Stimulation; Pyramidal Cells; Rats; Rats, Sprague-Dawley; Tissues; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1002418107

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.