, 2007, Tan et al., 2008, Lumacaftor supplier Benzekhroufa et al., 2009a, Benzekhroufa et al., 2009b and Tan et al., 2010; Table 2). An important caveat, however, is that

promoter specificity observed in one region of organism may not hold in other tissues or organisms, and promoter and tropism strategies are not truly generalizable. Additionally, promoter specificity must be accompanied by viral access: a given neuron must both express the viral receptor and the promoter in order to be specified in this manner. Where available, each promoter must be characterized for cell-type specificity within the context of the chosen viral vector, organism, and brain region. For simple optogenetic applications with small promoters, such as the expression of an opsin gene tagged with a fluorescent protein, AAV vectors are sufficient. However, expression of larger genes and larger promoters, or coexpression of more than one optogenetic tool, requires careful consideration when choosing the appropriate vector. The main challenge in achieving specific expression with viral targeting is that the genome size contained in a viral capsid is limited, depending on the virus type and serotype. For example, LV particles can carry a genome check details of up to 9 kb (Kumar

et al., 2001), including the regulatory elements and viral genes encoded within. AAV-based vectors are generally restricted to a genome size of 4.7 kb, although new methods might facilitate expression of larger genomes (Dong et al., 1996 and Dong et al., 2010). For expression of even larger genomes (e.g., with larger promoter fragments or transgenes), adenoviral vectors can carry up to 27 kb of genetic material (Soudais et al., 2004). Herpes simplex-based vectors (HSV; Lilley et al., 2001, Lima et al., 2009, Covington et al., 2010 and Lobo

et al., 2010) also have greater carrying capacity and offer the potential Non-specific serine/threonine protein kinase for transducing axon terminals more efficiently than LV or most AAV serotypes, although consistency and toxicity are concerns for HSV approaches (Fink et al., 1996). This axonal-transduction property (shared with rabies viruses, pseudotyped LVs, some AAVs, and pseudorabies viruses (Kaspar et al., 2002, Burger et al., 2004, Kato et al., 2007, Callaway, 2008, Miyamichi et al., 2011 and Kato et al., 2011) can be either a feature or a bug in a given optogenetic experimental paradigm. This property when utilized diminishes one of the valuable specificities of virus-based optogenetics, which has been confinement of opsin gene transduction to local cell bodies without the confound of transducing (and photosensitizing) incoming afferents (e.g., Lee et al., 2010). On the positive side, such “retrograde” transduction provides one means for targeting neurons based on connectivity (although other methods described below exist to achieve this goal).