NRG1 accelerates the forgetting of fear memories and facilitates the induction of long-term depression in adult mice

Rationale Forgetting of fear memory is a current medical therapy for posttraumatic stress disorder (PTSD), and hippocampal long-term depression (LTD) may be the underlying mechanism. Neuregulin 1 (NRG1), a trophic factor, reportedly modulates memory consolidation and synaptic plasticity. Methods Fear memory was assessed using contextual fear conditioning. Electrophysiology was used to measure LTD and GABAergic transmission in the hippocampus. Objectives To determine the contribution of hippocampal NRG1 to fear memory forgetting and low-frequency stimulation (LFS)-induced LTD. Results Administration of NRG1 in the hippocampus accelerated forgetting of contextual fear memories. Furthermore, NRG1 had no effect on low-frequency stimulation-induced LTD in young mice but significantly facilitated the induction of LTD and GABAergic transmission in adult animals. More importantly, NRG1-facilitated LTD induction in adult mice could be blocked by inhibition of GABA(A) receptors and NMDAR activation. Conclusion These findings suggest a role for NRG1 in fear memory forgetting and hippocampal LTD, providing a potential target for the development of drug-assisted PTSD therapy.