Distinct roles of NPTX1 and NPTX2 in synaptic transmission of the fear memory engrams in the dentate gyrus

Background The synaptic transmission of memory engrams is important for their roles in memory storage and retrieval, and can be regulated by multiple neuronal adhesion molecules. This study focuses on the roles of neuronal pentraxin (NPTX) family members (NPTX1 and NPTX2), which are biomarkers for cognitive decline, in the synaptic transmission of Fos-(F-RAM) and Npas4-(N-RAM)-dependent engrams formed during contextual fear conditioning in the dentate gyrus. Methods Utilizing robust activity marking (RAM) system, contextual fear conditioning, conditional knockout (cKO) technology and electrophysiological recording, we analyzed the characteristic of miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) in engram cells of wild-type and Nptxs cKO mice. Results Nptx1 cKO leads to an increased amplitude and frequency of mEPSCs and decreased amplitude of mIPSCs in F-RAM neurons, as well as an elevated mEPSC frequency and reduced mIPSC frequency in N-RAM neurons. In contrast, Nptx2 cKO results in a decreased mEPSC frequency and increased mIPSC frequency in both F-RAM and N-RAM neurons. Conclusion Nptx1 cKO increased engram activity while Nptx2 cKO decreased engram activity. These findings reveal the distinct roles of the NPTX family in regulating the synaptic transmission of the fear engrams.