Fear memories can persist a lifetime with conscious and non-conscious continuum. In spite of their stability, we still do not understand the molecular and circuit mechanism for the organization of fear memories in the brain. We are using the mouse model for simple cued-fear conditioning to tackle this fundamental question in systems neuroscience.

Our investigation is powered by novel genetic technologies. For example, we have developed and deployed virus-delivered inducible silencing for synaptic transmission (vINSIST) method for combinatorial targeting of different brain regions to silence synaptic output before and after cued-fear conditioning.  With the vINSIST method, we discovered that cued-fear memory is sequentially printed from the basolateral amygdala (BLA) to the medial prefrontal cortex (mPFC) and, subsequently, to the other brain region(s). By tagging fear-experience activated neurons using our novel genetic method, virus-delivered genetic activity-induced tagging of cell ensembles (vGATE), we have demonstrated that cued-fear memory can be flexibly retrieved from both BLA and mPFC.

We achieve insight into the molecular and cellular mechanism in play, we have investigated and discovered inter-regional postsynaptic-BLA and presynaptic-mPFC N-methyl-D-aspartate (NMDA) receptor as necessary components for cued-fear conditioning, which we hypothesize is mediated by activity-dependent anterograde-retrograde brain-derived neurotrophic factor signaling, thus acting as a “molecular-synaptic printer” for sequential brain-wide mapping of cued-fear memory engrams.