AAV1-Syn-Cre

The dorsal cochlear nucleus (DCN) is the first site of multisensory integration in the mammalian auditory pathway. DCN circuits integrate non-auditory information (e.g., position of the head and ears) with auditory cues, and this fusion may help determine the location of a sound source or inhibit the perception of self-generated sounds. Several extrinsic sources of these non-auditory cues have been described in various species, and among these are first- and second-order trigeminal axonal projections. There is evidence for the presence of these axonal projections in guinea pigs and rats, although the size of the pathways is smaller than necessary for prey survival. However, the lack of evidence for these projections in the mouse, an increasingly important species in auditory neuroscience, raises questions about the generalizability of these proposed functions. Here, researchers investigated the presence of trigeminal projections to the DCN in mice using viral and transgenic approaches. They found that the spinal trigeminal nucleus does project to the DCN, targeting granule cells and monopolar brush cells. However, direct axonal projections from the trigeminal ganglion itself were undetectable. Thus, in mice, secondary brainstem sources convey nonauditory signals to the DCN that can provide processed trigeminal signals to the DCN, but primary trigeminal afferents are not directly integrated by the DCN.

To determine the projection pattern of the trigeminal brainstem region, the researchers used the AAV1-Syn-Cre virus, which translocates from neurons at the injection site to its postsynaptic target. Following this monosynaptic presynaptic transfer, the virus expresses the Cre recombinase, which results in the expression of a fluorescent protein in Ai9 tdTomato reporter mice. AAV1-Syn-Cre was injected into the spinal trigeminal nucleus (SpV) of Ai9 mice (Figure 1A), and axonal projections of infected neurons were traced to their postsynaptic partners, as shown by clearly labeled tdTomato-positive fibers and cell bodies in the facial motor nucleus, superior colliculus, and thalamus (Figure 1B-D). This expression pattern confirmed that the SpV both projects to these regions and makes synaptic contacts in these regions. These results validate the validity of the transsynaptic labeling approach.

Figure 1. Spinal trigeminal nucleus injection labels expected targets. (Balmer T S, Trussell L O. 2021)