Postnatal NMDA receptor blockade increases expression of functional NR2B receptors in neocortical FSIs.

<p>Prototypical excitatory post-synaptic currents were evoked onto layer IV FSIs in a thalamocortical slice preparation. (A–C) AMPA-mediated responses were similar in vehicle-treated mice (black traces) and MK-801-treated mice (red traces). (V_Hold-AMPA = −60 mV). Traces shown are the average of 5–10 responses obtained at the same stimulus intensity from vehicle-treated mouse (black lines); or MK-801-treated mouse (red lines). Dashed boxes designate regions of interest in activation and decay kinetics. (D–F) Bar graphs of mean current amplitude and mean weighted activation tau (τ_wAct.) and deactivation tau (τ_wDeact.) of evoked AMPA current evoked from vehicle-treated mice (black bars) and MK-801-treated mice (red bars). (G, H) The kinetics of NMDA-mediated responses are slower in MK-801-treated mice (red traces). (V_Hold-NMDA = +60 mV). Traces shown are the average of 5–10 responses obtained at the same stimulus intensity. Dashed boxes designate regions of interest in activation and decay kinetics. (I–K) Bar graphs of mean current amplitude and mean weighted activation tau (τ_w) and deactivation tau (τ_w) of evoked NMDA current from vehicle and MK-801-treated mice. Values are means ± S.E.M. *<i>P</i><0.05, vs. control by ANOVA. (L–S) Representative confocal micrographs of layer IV somatosensory cortex from mice neonatally treated with vehicle (L–O), or MK-801 (P–S). (L, P) Dashed boxes designate regions of interest in layer IV selected for higher magnification as shown in (M–O), and (Q–S). Green = Parvalbumin; Red = GluN2B. Scale bars = 100 um (L, P) or 10 um (M–O; Q–S). Images are shown as a maximum intensity projection of single images at a Z-spacing of 1.0 uM. (N, R) Arrowheads denote GluN2B staining as puncta or broad staining in brain slices from a vehicle-treated, or MK-801-treated mouse, respectively. (T–W) Representative traces of ifenprodil blockade on monosynaptic NMDA current evoked onto a FSI from an adolescent mouse neonatally treated with vehicle (T) or MK-801 (V) Traces shown are averages of 5–10 responses to the same stimulus intensity before (black lines) and after (grey lines) 10 minute wash in of 3 uM Ifenprodil. (U, W) Same traces as shown in (T) and (V) scaled on y-axis to facilitate visual comparison of the actions of ifenprodil on activation and decay kinetics. Average traces were fit, as previously described. (X, Y, Z) Quantitative analysis of impact of ifenprodil on mean peak amplitude (X); mean reduction in total charge (Y); and mean change in τ_w decay (Z). (<i>N</i> = 4 cells from 4 animals (vehicle-treated); and 3 cells from 3 animals (MK-801-treated).