Abstract
The establishment of effective molecular interventions to improve memory and alleviate memory deficits in disease remains a long-standing challenge despite growing molecular understanding of synaptic plasticity and memory formation. Capitalizing on the fact that long-term potentiation (LTP) requires N-methyl-D-aspartate receptors (NMDARs) and Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα), we develop an intrabody that targets NMDARs and show that intrabody-mediated postsynaptic enrichment of CaMKIIα in the hippocampus improves contextual fear memory. This molecular approach suggests a potential demand for effective targeting of postsynaptic molecules to enhance memory and provides insights into studying memory improvement in health and disease.