Developmental changes in NMDA and non-NMDA receptor-mediated synaptic potentials in rat neocortex.

1. In vitro slices of frontal neocortex were prepared from rat pups 3-14 days of age. Whole-cell patch-clamp recordings were obtained from layer II-III cortical neurons, and measurements of passive membrane properties were made. The development of evoked synaptic excitation and inhibition was also examined with the use of current- and voltage-clamp techniques. 2. Pharmacological separation of excitatory synaptic activity into both N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated components was accomplished by application of D(-)2-amino-5-phosphonovaleric acid (APV), D(-)2-amino-7-phosphonoheptanoic acid (AP7), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Inhibitory synaptic events were described according to their reversal potentials and modulation by the GABAA receptor antagonist bicuculline methiodide (BMI). 3. Pups were grouped into three categories on the basis of age: postnatal day (PN) 3-5, PN 6-8, and PN 9-14. In slices from PN 3-5 pups, neurons exhibited high input resistances (Rn) and relatively low resting membrane potentials (RMP). Rns decreased, and RMPs became more negative with development. At all ages studied, current-voltage relationships measured in current clamp were relatively linear, with inward rectification observed in some neurons at hyperpolarized membrane potentials. Neurons in each group were capable of firing overshooting action potentials. 4. Local stimulation in layer IV-V at 0.033 Hz elicited depolarizing excitatory postsynaptic potentials (EPSPs) in neurons from all three age groups. In PN 3-5 neurons, EPSPs were characterized by a long duration and latency to peak. By PN 6-8, EPSPs had decreased significantly in both duration and latency-to-peak. Some neurons responded with a single-component EPSP, whereas others exhibited multicomponent EPSPs consisting of distinct early and late components. In PN 3-5 neurons, increasing the frequency of stimulation from 0.033 to 1 Hz resulted in an overall decrease in the amplitude of the entire EPSP, whereas in PN 6-8 neurons the main decrease was observed in the late EPSP. 5. Excitatory postsynaptic currents (EPSCs) recorded in both PN 3-5 and PN 6-8 neurons were shorter in duration than corresponding EPSPs and consisted of both early and late components. Early EPSCs routinely increased in amplitude with hyperpolarization at all ages. In PN 3-5 neurons, the voltage dependence of late EPSCs was variable. By PN 6-8, late EPSCs always exhibited a region of reduced amplitude from -45 to -90 mV. The reversal potential for both early and late EPSCs was near +10 mV.(ABSTRACT TRUNCATED AT 400 WORDS)