LRP4 is required for the olfactory association task in the piriform cortex

BACKGROUND: Low-density lipoprotein receptor-related protein 4 (LRP4) plays a critical role in the central nervous system (CNS), including hippocampal synaptic plasticity, maintenance of excitatory synaptic transmission, fear regulation, as well as long-term potentiation (LTP). RESULTS: In this study, we found that Lrp4 was highly expressed in layer II of the piriform cortex. Both body weight and brain weight decreased in Lrp4(ECD/ECD) mice without TMD (Transmembrane domain) and ICD (intracellular domain) of LRP4. However, in the piriform cortical neurons of Lrp4(ECD/ECD) mice, the spine density increased, and the frequency of both mEPSC (miniature excitatory postsynaptic current) and sEPSC (spontaneous excitatory postsynaptic current) was enhanced. Intriguingly, finding food in the buried food-seeking test was prolonged in both Lrp4(ECD/ECD) mice and Lrp4 cKO (conditional knockout of Lrp4 in the piriform cortex) mice. CONCLUSIONS: This study indicated that the full length of LRP4 in the piriform cortex was necessary for maintaining synaptic plasticity and the integrity of olfactory function. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-022-00792-9.