Emerging role of viral vectors for circuit-specific gene interrogation and manipulation in rodent brain

Over the past half century, novel tools have allowed the characterization of myriad molecular underpinnings of neural phenomena including synaptic function, neurogenesis and neurodegeneration, membrane excitability, and neurogenetics/epigenetics. More recently, transgenic mice have made possible cell type-specific explorations of these phenomena and have provided critical models of many neurological and psychiatric diseases. However, it has become clear that many critical areas of study require tools allowing the study and manipulation of individual neural circuits within the brain, and viral vectors have come to the forefront in driving these circuit-specific studies. Here, we present a surface-level review of the general classes of viral vectors used for study of the brain, along with their suitability for circuit-specific studies. We then cover in detail a new long-lasting, retrograde expressing form of herpes simplex virus termed LT-HSV that has become highly useful in circuit-based studies. We detail some of its current uses and propose a variety of future uses for this critical new tool, including circuit-based transgene overexpression, gene editing, and gene expression profiling.