Parietal-frontal pathway controls relapse of fear memory in a novel context

초록

The ability to process contextual stimuli to adapt rapidly to novel circumstances is fundamental for survival, but maladaptive information processing can cause fear-related disorders. However, it remains unknown how novel contextual stimuli are associated with fear. We demonstrate that the posteriorparietal cortex (PPC) to the anterior cingulate cortex (ACC) governs the relapse of extinguished fear memories in a novel context. We observed enhanced populational calcium activity in the ACC neurons that received projections from the PPC (PPC-ACC) and increased synaptic activity in the BLA-projecting PPC-ACC neurons upon renewal in a novel context, where excitatory postsynaptic currents amplitudes increased but inhibitory postsynaptic current amplitudes decreased. In addition, we found that parvalbumin (PV)-expressing interneurons (PPC-ACCPV) control novel context-dependent fear renewal, which was blocked by the chronic administration of fluoxetine, a first-line pharmacotherapy for post-traumatic stress disorder. Our findings highlight the PPC-ACC pathway as a potential therapeutic target for fear-related disorders.