The NMDA-to-AMPA Ratio at Synapses Onto Layer 2/3 Pyramidal Neurons Is Conserved Across Prefrontal and Visual Cortices

Abstract

To better understand regulation of N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor complements across the cortex, and to investigate NMDA receptor (NMDAR)-based models of persistent activity, we compared NMDA/AMPA ratios in prefrontal (PFC) and visual cortex (VC) in rat. Whole cell voltage-clamp responses were recorded in brain slices from layer 2/3 pyramidal cells of the medial PFC and VC of rats aged p16–p21. Mixed miniature excitatory postsynaptic currents (mEPSCs) having AMPA receptor (AMPAR)- and NMDAR-mediated components were isolated in nominally 0 Mg²⁺ ACSF. Averaged mEPSCs were well-fit by double exponentials. No significant differences in the NMDA/AMPA ratio (PFC: 27 ± 1%; VC: 28 ± 3%), peak mEPSC amplitude (PFC: 19.1 ± 1 pA; VC: 17.5 ± 0.7 pA), NMDAR decay kinetics (PFC: 69 ± 8 ms; VC: 67 ± 6 ms), or degree of correlation between NMDAR- and AMPAR-mediated mEPSC components were found between the areas (PFC: n = 27; VC: n = 28). Recordings from older rats (p26–29) also showed no differences. EPSCs were evoked extracellularly in 2 mM Mg²⁺ at depolarized potentials; although the average NMDA/AMPA ratio was larger than that observed for mEPSCs, the ratio was similar in the two regions. In nominally 0 Mg²⁺ and in the presence of CNQX, spontaneous activation of NMDAR increased recording noise and produced a small tonic depolarization which was similar in both areas. We conclude that this basic property of excitatory transmission is conserved across PFC and VC synapses and is therefore unlikely to contribute to differences in firing patterns observed in vivo in the two regions.