EF1a-ChR2-mCherry AAV (Serotype 9)

Not only are AAVs an extremely flexible, efficient, and reliable tool for delivering reporter genes to specific nodes of a circuit to understand the topology of neural circuits, but the ability to package elements into them in addition to fluorescent reporters is where they have truly revolutionized neuroscience research. While AAVs have a relatively limited packaging capacity of approximately 4.8 kb, the ability to encode a wide variety of proteins that can modulate circuit nodes provides the ability to temporally control neuronal function with extremely tight control and accuracy in real time.

Most notably, optogenetics and chemogenetics tools have revolutionized the ability to manipulate specific nodes, edges, and microcircuits. Optogenetics involves placing sequences for light-induced excitatory (e.g., Channelrhodopsin2, ChrimsonR, etc.) or inhibitory (e.g., Arch, eNpHR, etc.) ion channels within an AAV vector. This allows these channels to be inserted into the membrane following transduction with the viral vector, allowing researchers to use specific wavelengths of light to alter specific neuronal properties with extremely high temporal precision. Activation of these light-driven channels alters membrane potential dynamics and neurotransmitter release. This provides neuroscientists with the ability to use different wavelengths of light to modulate neuronal firing on microsecond timescales by either increasing or decreasing firing of neurons within nodes of interest.