Identification of dentate granule-cell-selective enhancer for AAV approach
(A) A schematic showing the regional sampling strategy for excitatory-neuron-specific single-cell RNA-seq (scRNA-seq) data in the hippocampus.10
(B) Of the target genes from previously identified enhancer-AAVs selectively targeting cortical excitatory neuron types,13Lratd2 showed the highest overall normalized expression in dentate gyrus (DG) granule cells in the dorsal hippocampus compared to other hippocampal excitatory neuron types.
(C) A plasmid containing three copies of a short core sequence of mscRE4 transcript were packaged into an AAV (PHP.eB) capsid for intracerebral injections in the DG to drive YFP expression.
(D and E) AAV.3x(core)mscRE4.YFP expression in DG granule cells after 1–2 weeks. Scale bars: 100 μm (D) and 50 μm (E).
v, ventral; d, dorsal; DG, dentate gyrus; mc, mossy cells; CA3, Cornu Ammonis 3; CA2, Cornu Ammonis 2; CA1, Cornu Ammonis 1; ML, molecular layer; GCL, granule cell layer.