Figure 6. Loss of NMDA receptors selectively from parvalbumin+ cells impacts SRP but not adult OD plasticity.

(A) VEPs recorded from mice in which the mandatory GluN1 subunit of the NMDA receptor was genetically ablated from PV+ cells using Cre recombinase technology (PV GluN1 KO, gray) were significantly greater in magnitude than those recorded from WT littermates (black), suggesting disinhibition of the visual response. In these same PV GluN1 KO mice, SRP was also significantly impacted as there is was significantly less gain in magnitude over days of repeated presentation of an X° stimulus than observed in WT littermates. (B) This significant reduction in the magnitude of SRP was most clearly observed if VEP magnitude was normalized to the magnitude on day 1. (C) After SRP, both PV GluN1 KO mice and their WT littermates exhibited a significantly greater VEP magnitude elicited by the now familiar stimulus than interleaved presentations of a novel oriented stimulus. However, consistent with the observed difference in magnitude on day 1, VEPs elicited by a novel X + 90° stimulus in PV GluN1 KO mice were significantly greater in magnitude than those in WT littermate mice. No significant difference was observed for VEPs elicited by the familiar stimulus. (D) A significant difference in the ratio of VEP magnitude elicited by the familiar and novel stimuli reveals a deficit in SRP expression in PV GluN1 KO mice. (E) In contrast, PV GluN1 KO mice exhibited a normal adult OD shift after 7 days of MD, resulting from open eye potentiation (yellow outlines). (F) Wild-type (WT) littermates exhibited the same significant open eye potentiation (yellow bars) after 7 days of MD. (G) A comparison of the degree of OD shift as a result of 7 days of MD reveals a significant shift in OD ratio in both genotypes but no difference between genotypes, indicating that NMDA receptors in PV+ cells are not required for induction or expression of the OD shift. (H) To confirm genetic ablation of NMDARs selectively from parvalbumin (PV+) neurons in the PV-GluN1 KO; mice were injected with an AAV5 vector to express GFP in a Cre-dependent fashion in PV+ cells only. After 1 month, fluorescence-guided intracellular recordings were performed from ex vivo slices of visual cortex. NMDAR-mediated synaptic transmission was normal in excitatory control cells but abolished in PV+ cells. This is expressed here as the NMDAR EPSC/AMPAR EPSC ratio in excitatory cells (black outline) and PV+ cells (green outline). Sample EPSC traces mediated by the AMPAR (downward) and NMDAR (upward) are shown at the top of the panel. Significant comparisons are marked with an asterisk throughout while non-significant comparisons are marked with n.s. Error bars are standard error of the mean (S.E.M.).

DOI: http://dx.doi.org/10.7554/eLife.11450.017