title: A feedback neural circuit for calibrating aversive memory strength.
abstract: Aversive experiences powerfully regulate memory formation, and memory strength is proportional to the intensity of these experiences. Inhibition of the neural circuits that convey aversive signals when they are predicted by other sensory stimuli is hypothesized to set associative memory strength. However, the neural circuit mechanisms that produce this predictive inhibition to regulate memory formation are unknown. Here we show that predictive sensory cues recruit a descending feedback circuit from the central amygdala that activates a specific population of midbrain periaqueductal gray pain-modulatory neurons to control aversive memory strength. Optogenetic inhibition of this pathway disinhibited predicted aversive responses in lateral amygdala neurons, which store fear memories, resulting in the resetting of fear learning levels. These results reveal a control mechanism for calibrating learning signals to adaptively regulate the strength of behavioral learning. Dysregulation of this circuit could contribute to psychiatric disorders associated with heightened fear responsiveness.
authors.affiliation: RIKEN Brain Science Institute, Laboratory for Neural Circuitry of Memory, Saitama, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ozawa
authors.affiliation: RIKEN Brain Science Institute, Laboratory for Neural Circuitry of Memory, Saitama, Japan.
authors.forename: Edgar A
authors.initials: EA
authors.lastname: Ycu
authors.affiliation: RIKEN Brain Science Institute, Laboratory for Neural Circuitry of Memory, Saitama, Japan.|Sant Longowal Institute of Engineering and Technology (SLIET), Electrical and Instrumentation Engineering Department, Sangrur, India.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.affiliation: RIKEN Brain Science Institute, Laboratory for Neural Circuitry of Memory, Saitama, Japan.|Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Yeh
authors.affiliation: National University of Sciences and Technology, Atta-ur-Rahman School of Applied Biosciences, Islamabad, Pakistan.
authors.forename: Touqeer
authors.initials: T
authors.lastname: Ahmed
authors.affiliation: RIKEN Brain Science Institute, Laboratory for Neural Circuitry of Memory, Saitama, Japan.
authors.forename: Jenny
authors.initials: J
authors.lastname: Koivumaa
authors.affiliation: RIKEN Brain Science Institute, Laboratory for Neural Circuitry of Memory, Saitama, Japan.|Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Johansen
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D066272:Basolateral Nuclear Complex / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D017207:Rats, Sprague-Dawley