Abstract
In the hippocampus, the classical pyramidal cell type of the subiculum acts as a primary output, conveying hippocampal signals to a diverse suite of downstream regions. Accumulating evidence suggests that the subiculum pyramidal cell population may actually be comprised of discrete subclasses. Here, we investigated the extent and organizational principles governing pyramidal cell heterogeneity throughout the mouse subiculum. Using single-cell RNA-seq, we find that the subiculum pyramidal cell population can be deconstructed into eight separable subclasses. These subclasses were mapped onto abutting spatial domains, ultimately producing a complex laminar and columnar organization with heterogeneity across classical dorsal-ventral, proximal-distal, and superficial-deep axes. We further show that these transcriptomically defined subclasses correspond to differential protein products and can be associated with specific projection targets. This work deconstructs the complex landscape of subiculum pyramidal cells into spatially segregated subclasses that may be observed, controlled, and interpreted in future experiments.
Highlights
To interpret the complexity of the brain, neuroscience has sought to deconstruct brain regions and circuits into elemental and interpretable cell types (Zeng and Sanes, 2017)
Using single-cell next-generation RNA sequencing, we found that subiculum pyramidal cells could be partitioned into eight subclasses
We identified cluster-specific marker genes for which Allen Mouse Brain Atlas coronal in situ hybridization (ISH) (Lein et al, 2007) images were available, and examined the spatial expression of these marker genes (Figure 3)
Summary
To interpret the complexity of the brain, neuroscience has sought to deconstruct brain regions and circuits into elemental and interpretable cell types (Zeng and Sanes, 2017). Evidence is emerging that suggests heterogeneity within classical cell types of the hippocampus may be an important feature for mediating hippocampal computation and function (Cembrowski et al, 2016a; Cembrowski et al, 2016b; Danielson et al, 2016; Igarashi et al, 2014; Knierim et al, 2014; Lee et al, 2015; Lee et al, 2014; Soltesz and Losonczy, 2018; Strange et al, 2014; Thompson et al, 2008) One of these classical cell types is the pyramidal cell type of the subiculum, which acts as an output from the hippocampus to a wide array of downstream targets (Aggleton and Christiansen, 2015; Naber and Witter, 1998). This work produces a multimodal deconstruction of a key brain region, and will serve as a foundation for continuing to unravel the cell-type-specific rules of cognition
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