Neuronal heterogeneity in the medial septum and diagonal band of Broca: classes and continua

The medial septum and diagonal band of Broca (MSDB) is known for its diverse populations of cholinergic, GABAergic, and glutamatergic neurons, each contributing to various cognitive processes. However, cell-specific manipulations within this region often result in incongruous behavioral outcomes and reach conflicting conclusions, likely because of a hitherto unknown molecular complexity in its cellular landscape. In this study, we employed single-cell RNA sequencing to thoroughly describe the heterogeneity of MSDB neurons. We confirmed previously established neuronal classes, found gene expression gradients within them and revealed genetically defined subclusters. Moreover, we characterized the genetic profiles of these neuronal subclusters and mapped their spatial distribution. Our analysis presents a comprehensive description of the heterogeneity of MSDB neurons, provides marker genes to target them, explains previous paradoxical results, and opens unexplored avenues to study the impact of neuromodulators in the basal forebrain.