Canine Adenovirus 2: A Natural Choice for Brain Circuit Dissection

Abstract

Canine adenovirus-2 (CAV) is a canine pathogen that has been used in a variety of applications, from vaccines against more infectious strains of CAV to treatments for neurological disorders. With recent engineering, CAV has become a natural choice for neuroscientists dissecting the connectivity and function of brain circuits. Specifically, as a reliable genetic vector with minimal immunogenic and cytotoxic reactivity, CAV has been used for the retrograde transduction of various types of projection neurons. Consequently, CAV is particularly useful when studying the anatomy and functions of long-range projections. Moreover, combining CAV with conditional expression and transsynaptic tracing results in the ability to study circuits with cell-and/or projectiontype specificity. Lastly, with the well-documented knowledge of viral transduction, new innovations have been developed to increase the transduction efficiency of CAV and circumvent its tropism, expanding the potential of CAV for circuit analysis.

Characterization of striatal dopamine projections across striatal subregions in behavioral flexibility

“…Consistent with the current work, a study investigating self-stimulation of dopamine terminals in NAc found that mice were flexible following reversal of the active nosepoke (Zell et al, 2020). Future work could explore the difference between stimulating cell bodies and terminals by employing retrograde tracing and intersectional approaches, including Canine adenovirus-2 (Lavoie & Liu, 2020), to perform optogenetics specifically targeting distinct dopamine projection populations (Lerner et al, 2015).…”

Targeting Noradrenergic Neurons of the Locus Coeruleus: A Comparison of Model Systems and Strategies

“…Consequently, the specificity of PRS×8 driven expression can likely be improved by using lower titers in the future. However, it is important to note that all these studies used PRS×8-controlled constructs in combination with recombinant adenoviruses 21 or canine adenovirus 2 (CAV-2) [22][23][24]36 , which have a different tropism than rAAV2/9 used in our study 41 . With respect to rAAVs, insufficient PRS×8 mediated transgene expression was reported with rAAV2/7 42 (~20.6 % efficacy), while robust expression was reported upon injection of rAAV2/9 35,43 .…”

Feasibility of Canine Adenovirus Type 2 (CAV2) Based Vector for the Locus Coeruleus Optogenetic Activation in Non-Transgenic Rats: Implications for Functional Studies

“…For instance, 0.25–0.5 µL of CAV2 spread on average by 200 µm from the center of the injection site, while 0.25 µL of rAAV2-retro spread four times more [ 3 , 54 ]. More restricted diffusion of CAV2 has been proved useful when studying small brain structures [ 55 ]. Whereas AAVs transduce neuron soma to express gene transcripts, CARs are predominantly located on the axon surface [ 29 ] making CAV2-based vectors more suitable for the retrograde transduction of selected neuron populations both in the forebrain and spinal cord [ 28 , 30 , 56 ].…”

“…Whereas AAVs transduce neuron soma to express gene transcripts, CARs are predominantly located on the axon surface [ 29 ] making CAV2-based vectors more suitable for the retrograde transduction of selected neuron populations both in the forebrain and spinal cord [ 28 , 30 , 56 ]. At the same time, it has been shown that CAV2 transduction is limited to some types of neurons or pathways [ 55 ], possibly due to the varying expression level of CARs in different neuron populations [ 57 , 58 ].…”