Conclusion
Transient hypofunction of NMDARs with MK-801 alters the synaptic transfer of information from the entorhinal cortex to the dentate gyrus. These changes impact the lateral and medial synapses, dysregulating presynaptic glutamate release, induction of LTD and LTP, and synaptic filtering. Consistent with these alterations, spatial discrimination that depends on pattern separation activity is hindered in the experimental group. These physiological and behavioral dysregulations might account for the reduced cognitive performance observed in schizophrenia. Given its therapeutic potential, future research should consider the modulation of the endocannabinoid system (i.e., CB1R, 2-AG, or MAGL activity) to restore the synaptic strength and cognitive abilities of individuals at higher risk of developing schizophrenia.