Targeting of NF-κB to dendritic spines is required for synaptic signaling and spine development

Erica C. Dresselhaus, Matthew C.H. Boersma, Mollie K. Meffert

Research output: Contribution to journalArticlepeer-review

Abstract

Long-term forms of brain plasticity share a requirement for changes in gene expression induced by neuronal activity. Mechanisms that determine how the distinct and overlapping functions of multiple activity-responsive transcription factors, including nuclear factor κB (NF-κB), give rise to stimulus-appropriate neuronal responses remain unclear. We report that the p65/RelA subunit of NF-κB confers subcellular enrichment at neuronal dendritic spines and engineer a p65 mutant that lacks spine enrichment (p65ΔSE) but retains inherent transcriptional activity equivalent to wild-type p65. Wild-type p65 or p65ΔSE both rescue NF-κB-dependent gene expression in p65-deficient murine hippocampal neurons responding to diffuse (PMA/ionomycin) stimulation. In contrast, neurons lacking spine-enriched NF-κB are selectively impaired in NF-κB-dependent gene expression induced by elevated excitatory synaptic stimulation (bicuculline or glycine). We used the setting of excitatory synaptic activity during development that produces NF-κB-dependent growth of dendritic spines to test physiological function of spine-enriched NF-κB in an activity-dependent response. Expression of wild-type p65, but not p65<SE, is capable of rescuing spine density to normal levels in p65-deficient pyramidal neurons. Collectively, these data reveal that spatial localization in dendritic spines contributes unique capacities to the NF-κB transcription factor in synaptic activity-dependent responses.

Original languageEnglish (US)
Pages (from-to)4093-4103
Number of pages11
JournalJournal of Neuroscience
Volume38
Issue number17
DOIs
StatePublished - Apr 25 2018

Keywords

  • Compartmentalization
  • Dendritic spine
  • Gene expression
  • NF-kappaB
  • Synaptic plasticity
  • Transcription

ASJC Scopus subject areas

  • Neuroscience(all)

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