In addition to its central role in learning and memory, N-methyl D-aspartate receptor (NMDAR)-dependent signaling regulates central glutamatergic synapse maturation and has been implicated in schizophrenia. We have transiently induced NMDAR hypofunction in infant mice during post-natal days 7-11, followed by testing fear memory specificity and presynaptic plasticity in the prefrontal cortex in adult mice. We show that transient NMDAR hypofunction during early brain development, coinciding with the maturation of cortical plasticity results in a loss of an endocannabinoid(eCB)-mediated form of long-term plasticity (eCB-LTD) at adult central glutamatergic synapses, while another form of presynaptic plasticity mediated by the metabotropic glutamate receptor 2/3 (mGluR2/3-LTD) remains intact. Mice with this selective impairment of presynaptic plasticity also showed deficits in fear memory specificity. The observed deficit in cortical presynaptic plasticity may represent a neural maladaptation contributing to network instability and abnormal cognitive functioning.
Neuropsychopharmacology accepted article preview online, 24 January 2014. doi:10.1038/npp.2014.15.

PMID:

 24457285
[PubMed – as supplied by publisher]