Brain-wide circuit-specific targeting of astrocytes.

Astrocytes are integral components of brain circuitry. They enwrap synapses, react to neuronal activity, and regulate synaptic transmission. Astrocytes are heterogeneous and exhibit distinct features and functions in different circuits. Selectively targeting the astrocytes associated with a given neuronal circuit would enable elucidation of their circuit-specific functions but has been technically challenging to date. Recently, we constructed anterograde transneuronal viral vectors based on yellow fever vaccine YFV-17D. Among them, the replication-incompetent YFV-Cre can selectively turn on reporter genes in postsynaptic neurons if the viral gene NS1 is expressed in postsynaptic neurons. Here we show that without exogenous expression of NS1 at the postsynaptic sites, locally injected YFV-Cre selectively turns on reporter genes in astrocytes in downstream brain regions. The targeting of astrocytes can occur across the whole brain but is specific for the neuronal circuits traced. Therefore, YFV-Cre provides a tool for selective genetic targeting of astrocytes to reveal their circuit-specific roles.