Different cortical regions processing distinct information, such as the hippocampus and the neocortex, share common cellular components and circuit motifs but form unique networks by modifying these cardinal units. Cortical circuits include diverse types of GABAergic interneurons (INs) that shape activity of excitatory principal neurons (PNs). Canonical IN types conserved across distinct cortical regions have been defined by their morphological, electrophysiological, and neurochemical properties. However, it remains largely unknown whether canonical IN types undergo specific modifications in distinct cortical regions and display “regional variants”. It is also poorly understood whether such phenotypic variations are shaped by early specification or regional cellular environment. The chandelier cell (ChC) is a highly stereotyped IN type, which innervates axon initial segments of PNs, and thus serves as a good model to address this issue. Here we show that Cadherin-6 (Cdh6), a homophilic cell adhesion molecule, is a reliable marker of ChCs and Cdh6-CreER mice (both sexes) provide genetic access to hippocampal ChCs (h-ChCs). We demonstrate that compared to neocortical ChCs (nc-ChCs), h-ChCs cover twice as much area and innervate twice as many PNs. Interestingly, a subclass of h-ChCs exhibits calretinin (CR) expression, which is not found in nc-ChCs. Furthermore, we find that h-ChCs appear to be born earlier than nc-ChCs. Surprisingly, despite the difference in temporal origins, ChCs display host region-dependent axonal/synaptic organization and CR expression when heterotopically transplanted. These results suggest that local cellular environment plays a critical role in shaping terminal phenotypes of regional IN variants in the hippocampus and the neocortex.
Regional Cellular Environment Shapes Phenotypic Variations of Hippocampal and Neocortical Chandelier Cells
Max Planck Florida Institute for Neuroscience
