Sez-6 proteins affect dendritic arborization patterns and excitability of cortical pyramidal neurons

Jenny M. Gunnersen, Mary H. Kim, Stephanie J. Fuller, Melanie De Silva, Joanne M. Britto, Vicki E. Hammond, Philip J. Davies, Steve Petrou, E. S. Louise Faber, Pankaj Sah, Seong-Seng Tan

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

Development of appropriate dendritic arbors is crucial for neuronal information transfer. We show, using seizure-related gene 6 (sez-6) null mutant mice, that Sez-6 is required for normal dendritic arborization of cortical neurons. Deep-layer pyramidal neurons in the somatosensory cortex of sez-6 null mice exhibit an excess of short dendrites, and cultured cortical neurons lacking Sez-6 display excessive neurite branching. Overexpression of individual Sez-6 isoforms in knockout neurons reveals opposing actions of membrane-bound and secreted Sez-6 proteins, with membrane-bound Sez-6 exerting an antibranching effect under both basal and depolarizing conditions. Layer V pyramidal neurons in knockout brain slices show reduced excitatory postsynaptic responses and a reduced dendritic spine density, reflected by diminished punctate staining for postsynaptic density 95 (PSD-95). In behavioral tests, the sez-6 null mice display specific exploratory, motor, and cognitive deficits. In conclusion, cell-surface protein complexes involving Sez-6 help to sculpt the dendritic arbor, in turn enhancing synaptic connectivity.
Original languageEnglish
Pages (from-to)621-639
Number of pages19
JournalNeuron
Volume56
Issue number4
DOIs
Publication statusPublished - 2007
Externally publishedYes

Fingerprint Dive into the research topics of 'Sez-6 proteins affect dendritic arborization patterns and excitability of cortical pyramidal neurons'. Together they form a unique fingerprint.

Cite this