Dopamine Regulation of Amygdala Inhibitory Circuits for Expression of Learned Fear

GABAergic signaling in the amygdala controls learned fear, and its dysfunction potentially contributes to posttraumatic stress disorder (PTSD). We find that sub-threshold fear conditioning leads to dopamine receptor D4-dependent long-term depression (LTD) of glutamatergic excitatory synapses by increasing inhibitory inputs onto neurons of the dorsal intercalated cell mass (ITC) in the amygdala. Pharmacological, genetic, and optogenetic manipulations of the amygdala regions centered on the dorsal ITC reveal that this LTD limits less salient experiences from forming persistent memories. In further support of the idea that LTD has preventive and discriminative roles, we find that LTD at the dorsal ITC is impaired in mice exhibiting PTSD-like behaviors. These findings reveal a novel role of inhibitory circuits in the amygdala, which serves to dampen and restrict the level of fear expression. This mechanism is interfered with by stimuli that give rise to PTSD and may also be recruited for fear-related psychiatric diseases.