AAV11 mediates efficient retrograde trans-neuronal transduction of astrocytes

Understanding the mechanisms by which astrocytes regulate neural circuits is crucial for elucidating the mechanisms underlying cognitive and behavioral abnormalities in psychiatric disorders and for exploring potential therapeutic or intervention strategies. Viral tracers are powerful vehicles for comprehending the complex relationship between neurons and astrocytes. Despite adeno-associated virus 1 (AAV1) based anterograde trans-neuronal tools have been successfully applied for identifying astrocytes connected with presynaptic neurons, analogous retrograde trans-neuronal tools for labeling astrocytes connected to postsynaptic neurons remain under development. Here, we first demonstrate that GfaABC1D promoter embedding AAV11 can transfer retrogradely from axons of postsynaptic neurons to astrocytes. Furthermore, we established an AAV11-based dual-viral recombination strategy for labeling astrocytes connected to specific postsynaptic neurons. Finally, by employing targeted neuronal ablation technology to ablate neurons in a specific brain region, we observed that injection of AAV11 into the downstream brain region of this targeted area exhibited minimal labeling of astrocytes functionally associated with the ablated neurons. This finding indicates that AAV11 holds utility for deciphering pathological alterations in disease-related astrocyte-neuron connectivity networks. This work fills a key gap in tools used for studying astrocyte-neuron connectivity networks.