Others have shown brain-wide viral transduction of neurons from intraventricular injection of AAVs in P0-1 mice (e.g. Kim et al., EJN, 2013), but even the most effective AAV8 did not penetrate cortical interneurons well.
Is this a matter of serotype or promoter? In our hands, AAV9 also biases towards excitatory neurons and glia after P1 injection, whereas others (AAV1, AAV5, AAV2) did not penetrate parenchyma well, if at all. (all used CMV promoter).
I would like to achieve viral transduction of global interneurons, but cell specificity is not important as I am using a cre-driver line. Would i be better using hSyn or Dlx promoters? Does anyone have alternative strategies for postnatal delivery? Or is in utero electroporation my only option? (we are not currently set-up for this).
Many thanks!
Corey Fee
Hi Corey,
I have never done this personally, but I stumbled upon this preprint from the Gradinaru lab after multiple frustrated attempts at driving brain-wide recombination after intraventricular injection at P0.
Check it out, it may help!
Alberto - thank you so much. This sent me down a rabbit hole to what I believe will be an acceptable solution. This group has engineered highly effective AAVs that achieve good cortical/hpc transduction from simple retro-orbital injections in adult mice (PMID: 28671695). It looks like their enhanced AAV-PHP.eB is available via AddGene, and on top of this, it looks like other groups have achieved good interneuron transduction ( PMID: 28521139).
I will look into this further, but appreciate you bringing this to my attention.
All the best,
Corey
Hi Corey,
You can also may find insights here:
Article Lentiviral expression of GAD67 and CCK promoter-driven opsin...
Regards
Nicolas