The most prominent structural hallmark of the mammalian neocortical circuitry is the layer-based organization of specific cell types and synaptic inputs. Accordingly, cortical inhibitory interneurons (INs), which shape local network activity, exhibit subtype-specific laminar specificity of synaptic outputs. However, the underlying molecular mechanisms remain unknown. Here, we demonstrate that Immunoglobulin Superfamily member 11 (IgSF11) homophilic adhesion proteins are preferentially expressed in one of the most distinctive IN subtypes, namely, chandelier cells (ChCs) that specifically innervate axon initial segments of pyramidal neurons (PNs), and their synaptic laminar target. Loss-of-function experiments in either ChCs or postsynaptic cells revealed that IgSF11 is required for ChC synaptic development in the target layer. While overexpression of IgSF11 in ChCs enlarges ChC presynaptic boutons, expressing IgSF11 in nontarget layers induces ectopic ChC synapses. These findings provide evidence that synapse-promoting adhesion proteins, highly localized to synaptic partners, determine the layer-specific synaptic connectivity of the cortical IN subtype.
IgSF11 homophilic adhesion proteins promote layer-specific synaptic assembly of the cortical interneuron subtype
IgSF11 in ChCs is necessary for morphological, structural, and functional development of ChC presynaptic boutons on AISs of uL2/3 PNs. (A) Schematic
illustration of IgSF11 LOF experiments in ChCs. (B and C) Representative images of IgSF11 het (B) and homo (C) KO ChCs at EP21. Scale bars, 50 and 5 um (insets). (D to
F) Quantification of the total number of AIS boutons (D), the number of boutons per AIS (E), and the size of AIS boutons (F) in IgSF11 het and homo KO ChCs. n = 10 cells
from five mice per condition.
Max Planck Florida Institute for Neuroscience
