IgSF11 homophilic adhesion proteins promote layer-specific synaptic assembly of the cortical interneuron subtype

Yasufumi Hayano, Yugo Ishino, Jung Ho Hyun, Carlos G. Orozco, André Steinecke, Elizabeth Potts, Yasuhiro Oisi, Connon I. Thomas, Debbie Guerrero-Given, Eunjoon Kim, Hyung Bae Kwon, Naomi Kamasawa, Hiroki Taniguchi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbereabf1600
JournalScience Advances
Volume7
Issue number29
DOIs
StatePublished - Jul 2021

ASJC Scopus subject areas

  • General

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