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Dynamic Network Connectivity (DNC)

NMDA-NR2B Receptors Mediate Synaptic Communication in Layer III Pyramidal Cell Circuits

Our recent iontophoretic studies have shown that the persistent firing of dlPFC Delay neurons is highly dependent on NMDA receptors, including those with NR2B subunits. These NMDA receptos are found exclusively within the synapse, and are not extrasynaptic as they are in hippocampus. Iontophoresis of an NMDA-NR2B receptor blocker markedly reduced persistent firing (shown in red), while iontophoresis of an AMPA antagonist had much more subtle effects (green). In contrast, Response cells showed loss of firing to AMPA blockade (not shown). These physiological data are consistent with computational models by Xiao-Jing Wang predicting that persistent neuronal firing requires the slower kinetics of the NR2B receptor, while the faster kinetics of the AMPA receptor cause network collapse.

If you are interested: Wang MJ, Yang Y, Wang CJ, Gamo NJ, Jin LE, Mazer JA, Morrison JH, Wang X-J, Arnsten AF (2013) NMDA receptors subserve working memory persistent neuronal firing In dorsolateral prefrontal cortex. Neuron 77: 736-749

The Effects of Systemic Administration of Ketamine

Systemic administration of the NMDA antagonist, ketamine, impaired working memory performance and reduced Delay cell firing. However, ketamine increased the firing of post-saccadic Response cells, similar to that seen in rodents. Thus, dlPFC neurons do not respond in a unitary way to systemic ketamine administration. This information should be kept in mind when viewing fMRI data in humans.