Monosynaptic inputs to ErbB4-expressing inhibitory neurons in mouse primary somatosensory cortex.

Previous reports have described inputs to the somatosensory cortex (S1) in mouse or rat using retrograde or anterograde tracers. Such studies do not, however, reveal which particular cell types within the S1 cortex receive direct monosynaptic connections from these input sources. Here we describe the monosynaptic inputs to a subpopulation of mouse S1 inhibitory neurons that express ErbB4. We used a previously described "bridge protein," composed of the ErbB4 ligand, neuregulin (NRG1), fused to the avian viral receptor TVB (TVB-NRG1), along with EnvB pseudotyped lentivirus (LV) and rabies virus (RV), to selectively coinfect ErbB4-expressing neurons (Choi et al. [2010] Proc Natl Acad Sci U S A 107:16703-16708). The RV had its glycoprotein gene deleted and replaced with mCherry, so that infected cells express mCherry and the virus cannot spread without provision of rabies glycoprotein (RG) by transcomplementation. The LV encoded and expressed RG to allow transcomplementation in coinfected neurons, so that the RV could spread transsynaptically and label their direct monosynaptic inputs. The RV could not spread beyond the direct inputs, due to the lack of RG in presynaptic cells. This method revealed long-range connections from thalamus, nucleus basalis, raphe, and distant cortical areas, including ipsilateral motor, secondary somatosensory, retrosplenial, and perirhinal cortex and contralateral S1. In addition, local connections from ipsilateral pyramidal neurons within S1 were labeled. These input sources account for all of the known inputs to S1 described with standard tracers, suggesting that the subpopulation of ErbB4-positive inhibitory neurons infected using the TVB-NRG1 bridge protein receives inputs indiscriminately from S1 input sources.