Flow cytometry has proven its capability for rapid and quantitative analysis of individual cells and the separation of targeted biological samples from others. The emerging microfluidics technology makes it possible...

Background: Drug memory that generally develops with drug-paired contextual stimuli and drug administration is critical for the development, persistence and relapse of drug addiction. Previous studies have suggested that adult hippocampal neurogenesis (AHN) plays a role in cocaine memory formation; however, the underlying mechanism is not fully understood.Methods: Conditioned place preference (CPP), self-administration and locomotor activity were used to investigate the role of Tau in cocaine-associated memory formation. Virus-mediated gene transfer, western blot, immunohistochemistry, flow cytometry analysis, Tau-interacting proteomics, co-immunoprecipitation, and mutation of 4R Tau were performed. Results: Hippocampal expression of Tau was significantly decreased during the cocaine-associated memory formation. Genetic overexpression of four microtubule-binding repeats Tau (4R Tau) in the hippocampus disrupted cocaine memory by suppressing AHN. Furthermore, 4R Tau directly interacted with phosphoinositide 3-kinase (PI3K)-p85 and impaired its nuclear translocation and PI3K-AKT signaling, processes required for hippocampal neuron proliferation. Conclusions: 4R Tau modulates cocaine memory formation by disrupting AHN, suggesting a novel mechanism underlying cocaine memory formation and provide a new strategy for the treatment of cocaine addiction.