Fig. 2: The cellular basis of mental representation by the primate dlPFC.

A The firing patterns of a Delay cell in the rhesus monkey dlPFC during the oculomotor spatial delay response task, representing the 270° location in visual space. The neuron exhibits persistent firing across the delay epoch to the memory of a cue that had been presented at 270°, but not for other locations. B Iontophoresis of a drug that blocks NMDAR- GluN2B erodes the neuron’s ability to generate and sustain a mental representation of space. C A working model of the microcircuitry in deep layer III of dlPFC, with extensive recurrent excitation to generate persistent firing, and lateral inhibition from PV-containing interneurons to refine the contents of working memory. D A summary diagram of what is currently known about neurotransmission in deep layer III dlPFC recurrent excitatory synapses on spines, relying heavily on NMDAR, including those with GluN2B subunits, and cholinergic stimulation of nicotinic α7 receptors (Nic- α7R) to permit NMDAR actions by relieving the magnesium (Mg2+) block in the NMDAR pore. Muscarinic M1R also appear to contribute, e.g., by closing KCNQ potassium channels to depolarize the postsynaptic density (PSD). Both NMDAR- GluN2B and Nic-α7R flux high amounts of calcium (Ca2+), which may also help to depolarize the synaptic membrane.