Fig. 1.

α5 overexpression reduces tonic currents and firing rates in vHipp pyramidal cells. The placement of virus injections are indicated on a schematic of a coronal section through the vHipp. Circles indicate injections of the control virus. Squares indicate injections of the GABA_A virus. Immunohistochemistry for GFP was used to confirm transgene expression in the vHipp. Representative images are shown in a. To verify that gene expression was confined primarily to CAMKII-positive pyramidal cells, we also performed dual-labelling for GFP and CAMKII. Representative images are shown in b. Overexpression of the α5, but not the α1, subunit of the GABA_A receptor increased tonic GABA currents (c). Neither α1 nor α5 overexpression affected IPSC frequency or amplitude (c). Representative traces are shown in d. A representative GFP-positive cell is depicted in e. A subset of recorded cells were labeled with neurobiotin and a representative image of a neurobiotin-labeled pyramidal cell is shown in f. Scale bars are 20 microns unless otherwise labeled. Asterisk is significantly different than control using One-way ANOVA and Holm–Sidak tests. n = 6–9 cells per group. Extracellular electrophysiology was used to measure the firing rates of putative pyramidal cells in the vHipp. In the MAM model of schizophrenia, there is an increase in pyramidal cell firing rate, which is completely abolished by overexpression of the α5, but not α1 subunit of the GABA_A receptor (g). Representative traces are shown in h. Scale bar is 5 s. Asterisk is significantly different than saline/control; +plus is significantly different than MAM/control using Two-Way ANOVA and Holm–Sidak tests. n = 43–62 cells per group. Data are shown as mean ± SEM