BLA DBS improves anxiety and fear by correcting weakened synaptic transmission from BLA to adBNST and CeL in a mouse model of foot shock.

Abstract

Deep brain stimulation (DBS) in the basal lateral amygdala (BLA) has been established to correct symptoms of refractory post-traumatic stress disorder (PTSD). However, how BLA DBS operates in correcting PTSD symptoms and how the BLA elicits pathological fear and anxiety in PTSD remain unclear. Here, we discover that excitatory synaptic transmission from the BLA projection neurons (PNs) to the adBNST, and lateral central amygdala (CeL) is greatly suppressed in a mouse PTSD model induced by foot shock (FS). BLA DBS revises the weakened inputs from the BLA to these two areas to improve fear and anxiety. Optogenetic manipulation of the BLA-adBNST and BLA-CeL circuits shows that both circuits are responsible for anxiety but the BLA-CeL for fear in FS mice. Our results reveal that synaptic transmission dysregulation of the BLA-adBNST or BLA-CeL circuits is reversed by BLA DBS, which improves anxiety and fear in the FS mouse model.