Targeted gene delivery to telencephalic inhibitory neurons by directional in utero electroporation

Abstract

Telencephalic inhibitory neurons originate in the ganglionic eminences and migrate to the cerebral cortex following a tangential trajectory, before they differentiate and integrate within the local circuitry. Current studies of interneuron development and function benefit from the use of knock-out and transgenic mice, whereas none take advantage of the versatility of in utero electroporation. Here, we show how in utero electroporation can be directed to the ganglionic eminences to specifically target gene expression to interneurons. Electroporation of GFP-encoding plasmids into the ganglionic eminences results in selective labeling of migrating interneurons during development. In the adult brain of electroporated animals, a wide variety of cortical, hippocampal and olfactory bulb interneurons are labeled. We also show that GFP-expressing interneurons can be visualized in living slices of adult cerebral cortex, where they display normal electrophysiological properties. Photostimulation studies using acute slices show that cortical GFP+ interneurons receive normal, layer-specific synaptic input, indicating that these neurons integrate within the local cortical circuitry. Ganglionic eminence-directed in utero electroporation is therefore an effective, rapid, and versatile method of selectively transfecting telencephalic interneurons, optimal for both developmental studies and adult functional studies.