Auditory fear memory retrieval requires BLA-LS and LS-VMH circuitries via GABAergic and dopaminergic neurons

Fear and associated learning and memory are critical for developing defensive behavior. Excessive fear and anxiety are important components of post-traumatic stress disorder. However, the neurobiology of fear conditioning, especially tone-related fear memory retrieval, has not been clearly defined, which limits specific intervention development for patients with excessive fear and anxiety. Here, we show that auditory fear memory retrieval stimuli activate multiple brain regions including the lateral septum (LS). Inhibition of the LS and the connection between basolateral amygdala (BLA) and LS or between LS and ventromedial nucleus of the hypothalamus (VMH) attenuates tone-related fear conditioning and memory retrieval. Inhibiting GABAergic neurons or dopaminergic neurons in the LS also attenuates tone-related fear conditioning. Our data further show that fear conditioning is inhibited by blocking orexin B signaling in the LS. Our results indicate that the neural circuitries BLA-LS and LS-VMH are critical for tone-related fear conditioning and memory retrieval, and that GABAergic neurons, dopaminergic neurons and orexin signaling in the LS participate in this auditory fear conditioning.