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.