The Neurotrophic Receptor Tyrosine Kinase in MEC-mPFC Neurons Contributes to Remote Memory Consolidation

The PFC is thought to be the region where remote memory is recalled. However, the neurotrophic receptors that underlie the remote memory remain largely unknown. Here, we benefited from auto-assembly split Cre to accomplish the neural projection-specific recombinase activity without spontaneous leakage. Deletion of tropomyosin receptor kinase B (TrkB) in neurons projecting from the medial entorhinal cortex to the mPFC displayed reduced remote memory recall from the male mice, but the recent recall was intact. We found that the TrkB deletion attenuates the participation of mPFC cells in the remote fear memory recall. The disruption of remote recall was attributed to reduced reactivation of cells in the mPFC. Notably, TrkB deletion seriously inhibited experience-dependent maturation of oligodendroglia in the PFC, resulting in defects in remote recall that were rescued by clemastine administration. Together, our data suggest that TrkB in intercortical circuits functions in remote memory consolidation. SIGNIFICANCE STATEMENT Retrieving the past experiences or events is essential for the ones to lead life. The investigations performed in the rodent model have disclosed that the systems consolidation of memory accompanying changes of cortical circuits and transcriptome is required for maintaining the memory for a long time. In this study, the split Cre with TrkB(flox/flox) mice were subjected to discover that TrkB in the neurons plays a role in remote memory consolidation. We evaluated the contextual fear memory and labeled cells, which revealed deletion of TrkB interrupts newborn oligodendrocyte and reactivation of cells in mPFC at remote recall. Our data provide the implication that remote memory is relevant to neurotrophic receptor signaling as well as its influence on non-neuronal cells.