• J Pilli and S S Kumar.
• Department of Biomedical Sciences, College of Medicine & Program in Neuroscience, Florida State University, 1115 W. Call Street, Tallahassee, FL 32306-4300, United States.
• Neuroscience. 2014 Jul 11;272:271-85.

AbstractN-methyl-d-aspartate receptors (NMDARs) at layer (L)1/primary whisker motor cortex synaptic inputs are distinct from thalamic/striatal (Str) synaptic inputs onto L5 pyramidal neurons in the rat somatosensory cortex. However, the consequences of differential expression of putative GluN3A-containing triheteromeric NMDARs at L1 inputs and GluN2A-containing diheteromeric NMDARs at Str inputs on plasticity of the underlying synapses at the respective inputs remain unknown. Here we demonstrate that L1, but not Str, synapses are potentiated following delta burst stimulation (dBS). This potentiation is blocked by d-serine and/or intracellular 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) suggesting that it is subunit-specific and dependent on elevations in intracellular Ca(2+). Interestingly, ifenprodil, the GluN2B-preferring antagonist, suppresses baseline L1 responses but does not prevent induction of dBS-evoked potentiation. Unlike L1, Str synapses are maximally potentiated following theta burst stimulation (tBS) and this potentiation is blocked with BAPTA and/or the GluN2A-preferring antagonist NVP-AAM077. We show further that while dBS is both necessary and sufficient to potentiate L1 synapses, tBS is most effective in potentiating Str synapses. Our data suggest distinct potentiating paradigms for the two convergent inputs onto pyramidal neurons in the somatosensory cortex and co-dependence of synaptic potentiation on brain wave-tuned frequencies of burst stimulation and subunit composition of underlying NMDARs. A model for predicting the likelihood of enhancing synaptic efficacy is proposed based on Ca(2+) influx through these receptors and integration of EPSPs at these inputs. Together, these findings raise the possibility of input-specific enhancements of synaptic efficacy in neurons as a function of the animal's behavioral state and/or arousal in vivo.Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

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