Selective Control of Fear Expression by Optogenetic Manipulation of Infralimbic Cortex after Extinction.
Evidence from rodent and human studies has identified the ventromedial prefrontal cortex, specifically the infralimbic cortex (IL), as a critical brain structure in the extinction of conditioned fear. However, how IL activity controls fear expression at the time of extinction memory retrieval is unclear and controversial. To address this issue, we used optogenetics to precisely manipulate the activity of genetically targeted cells and to examine the real-time contribution of IL activity to expression of auditory-conditioned fear extinction in mice. We found that inactivation of IL, but not prelimbic cortex, impaired extinction retrieval. Conversely, photostimulation of IL excitatory neurons robustly enhanced the inhibition of fear expression after extinction, but not before extinction. Moreover, this effect was specific to the conditioned stimulus (CS): IL activity had no effect on expression of fear in response to the conditioned context after auditory fear extinction. Thus, in contrast to the expectation from a generally held view, artificial activation of IL produced no significant effect on expression of non-extinguished conditioned fear. Therefore, our data provide compelling evidence that IL activity is critical for expression of fear extinction and establish a causal role for IL activity in controlling fear expression in a CS-specific manner after extinction.
Department of Biological Sciences, KAIST Institute for the BioCentury (KIB), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.|Center for Functional Connectomics, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, Korea.
Hyung-Su
HS
Kim
Department of Biological Sciences, KAIST Institute for the BioCentury (KIB), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Hye-Yeon
HY
Cho
Center for Functional Connectomics, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, Korea.|Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.|Institute of Molecular and Cell Biology, Singapore, Singapore.
George J
GJ
Augustine
Department of Biological Sciences, KAIST Institute for the BioCentury (KIB), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Jin-Hee
JH
Han
D000161:Acoustic Stimulation; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D062308:Optogenetics; D017397:Prefrontal Cortex / Q000502:physiology*
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2