Stereotaxic Injection of Lentiviral Vectors into the Primate Brain

Nonhuman primates (NHPs) have been widely and crucially utilized as model animals for understanding mechanisms of various higher brain functions and pathomechanisms of neurological and psychiatric disorders, since their behaviors mimic those of humans in both normal and pathological states. To know how complex neural networks are involved in such behavioral states, it is essential to define the causal roles of specific pathways and neuron types that constitute these networks. Considering that genetically modified animals to be created through reproductive engineering are not commonly or readily available in NHPs, the gene transduction strategy via viral vectors is the only effective approach to the development of primate models. For this purpose, lentiviral vectors and adeno-associated virus vectors are mainly used. The ability of lentiviral vectors to insert longer sequences is advantageous for achieving cell-type-specific gene expression with the aid of promoters and enhancers. In addition, the use of envelopes that are derived from viruses exhibiting peculiar infection patterns or those being artificially modified is a powerful method for introducing foreign genes into specific cell populations. Furthermore, semipermanent gene expression via lentiviral vectors is an attractive feature for translational gene therapy research. This chapter will outline the stereotaxic injection of lentiviral vectors into the primate brain, primarily for neural network analysis.