Finally, we asked what other genes were co-expressed with alpha subunits associated with fast-firing (Figure S3E). This collection contained Neurofilament genes (Figure 3), ion channels (e.g. Hcn2), and unexpected genes, such as the transcription factor Foxj1 and the creatine transporter Slc6a8. Indeed, expression of Slc6a8 and Hcn2 were strongly correlated and high in fast-firing cell types (Figure 4E). Our data suggest human neurological symptoms associated with Slc6a8 mutations (van de Kamp et al., 2013) may in part be due to deficits in fast-firing neurons, consistent with cortical GABAergic synapse loss observed in mouse models (Baroncelli et al., 2017). Gene co-expression relationships across large numbers of cell types yield new hypotheses about genes, brain circuitry, and disease.
