title: Basomedial amygdala mediates top-down control of anxiety and fear.
abstract: Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharmacologically, but respond to cognitive therapies. There has therefore been interest in identifying relevant top-down pathways from cognitive control regions in medial prefrontal cortex (mPFC). Identification of such pathways could contribute to our understanding of the cognitive regulation of affect, and provide pathways for intervention. Previous studies have suggested that dorsal and ventral mPFC subregions exert opposing effects on fear, as do subregions of other structures. However, precise causal targets for top-down connections among these diverse possibilities have not been established. Here we show that the basomedial amygdala (BMA) represents the major target of ventral mPFC in amygdala in mice. Moreover, BMA neurons differentiate safe and aversive environments, and BMA activation decreases fear-related freezing and high-anxiety states. Lastly, we show that the ventral mPFC-BMA projection implements top-down control of anxiety state and learned freezing, both at baseline and in stress-induced anxiety, defining a broadly relevant new top-down behavioural regulation pathway.
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|CNC Program, Stanford University, Stanford, California 94304, USA.
authors.forename: Avishek
authors.initials: A
authors.lastname: Adhikari
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|CNC Program, Stanford University, Stanford, California 94304, USA.
authors.forename: Talia N
authors.initials: TN
authors.lastname: Lerner
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Finkelstein
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Pak
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|CNC Program, Stanford University, Stanford, California 94304, USA.
authors.forename: Joshua H
authors.initials: JH
authors.lastname: Jennings
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|CNC Program, Stanford University, Stanford, California 94304, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Davidson
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|Neurosciences Program, Stanford University, Stanford, California 94305, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Ferenczi
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|Neurosciences Program, Stanford University, Stanford, California 94305, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Gunaydin
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Julie J
authors.initials: JJ
authors.lastname: Mirzabekov
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|CNC Program, Stanford University, Stanford, California 94304, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|Neurosciences Program, Stanford University, Stanford, California 94305, USA.
authors.forename: Sung-Yon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Lei
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|CNC Program, Stanford University, Stanford, California 94304, USA.|Neurosciences Program, Stanford University, Stanford, California 94305, USA.|Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA.|Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000503:physiopathology* / Q000523:psychology; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology* / Q000523:psychology; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D007858:Learning / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000502:physiology*; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology