Fig. 5.

Enhancement of tonic currents mediated by δ subunit-containing GABA_ARs decreases excitotoxic cell swelling of MSNs. (A–D). Illustrative IR-DIC images of wild-type striatal MSN obtained using a 40× objective show the MSNs before (A) and 10 min after exposure 50 μM NMDA (B) show the swelling and indistinct outlines after NMDA exposure in aCSF (n =17 cells from six slices in three mice). Images from slices in which tonic inhibition was selectively enhanced by a 5 min perfusion of 50 nM muscimol before (C) and during the 10 min exposure to 50 μM NMDA (D) show that muscimol decreases NMDA induced swelling in MSNs (n =36 cells from 10 slices in four mice). Insets show outlines used to measure the area and perimeter of the cells indicated by arrows. (E–H). Images of striatal MSNs from Gabrd^−/− mice before (E) and 10 min after exposure 50 μM NMDA (F) show the NMDA induced swelling (n =34 cells from nine slices in three mice). Images obtained following enhancement of tonic inhibition by muscimol before (G) and during the 10 min exposure to NMDA (H) show that muscimol does not protect against NMDA induced swelling of MSNs in Gabrd^−/− mice (n =41 cells from 10 slices in three mice). Insets show outlines used to measure the area and perimeter of the cells indicated by the arrows. Scale bar in (A) represents 10 μm. (I) Summary histogram shows the degree of NMDA induced increase in cell area in wild-type and Gabrd^−/− mice in the absence and presence of muscimol. Asterisk denotes a statistically significant (P<0.05) difference.