Figure 4.

Intrahippocampal delivery of a VGLUT1-targeting lentiviral shRNA vector appears to reduce VGLUT1 expression in neurons adjacent to the injection tract. (a) Representative low-power images of immunohistochemical staining for VGLUT1 (DAB; brown) in the dorsal hippocampus 27 days after administration of control nontargeting shRNA (left) or VGLUT1-targeting shRNA (right). Nuclei are counterstained with hematoxylin (purple). Asterisks positioned to the left of the needle tract illustrate the location of the higher-power images of (b) the CA1 stratum lacunosum-moleculare and (c) the polymorphic cell layer of the dentate gyrus. Arrowheads indicate the apparent visual boundary of reduced VGLUT1 expression following administration of the VGLUT1-targeting shRNA vector. However, signal intensity in a 20 × 25 μm area of stratum lacunosum-moleculare positioned 30 μm from the center of the injection tract (and normalized to an equivalent area 100 μm from the injection tract in the same slice) was significantly reduced by the VGLUT1-targeting vector (0.92±0.01 compared with 1.0±0.02 in controls; P<0.05). Scale bar: (a) 100 μm; (b, c) 50 μm. DG, dentate gyrus; g, granule cell layer; l, stratum lacunosum-moleculare; m, molecular layer; p, polymorphic cell layer; r, stratum radiatum. A full color version of this figure is available at the Neuropsychopharmacology, journal online.