| First Author | Boersma MC | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 14 | Pages | 5414-25 |
| PubMed ID | 21471377 | Mgi Jnum | J:183349 |
| Mgi Id | MGI:5318443 | Doi | 10.1523/JNEUROSCI.2456-10.2011 |
| Citation | Boersma MC, et al. (2011) A requirement for nuclear factor-kappaB in developmental and plasticity-associated synaptogenesis. J Neurosci 31(14):5414-25 |
| abstractText | Structural plasticity of dendritic spines and synapses is a fundamental mechanism governing neuronal circuits and may form an enduring basis for information storage in the brain. We find that the p65 subunit of the nuclear factor-kappaB (NF-kappaB) transcription factor, which is required for learning and memory, controls excitatory synapse and dendritic spine formation and morphology in murine hippocampal neurons. Endogenous NF-kappaB activity is elevated by excitatory transmission during periods of rapid spine and synapse development. During in vitro synaptogenesis, NF-kappaB enhances dendritic spine and excitatory synapse density and loss of endogenous p65 decreases spine density and spine head volume. Cell-autonomous function of NF-kappaB within the postsynaptic neuron is sufficient to regulate the formation of both presynaptic and postsynaptic elements. During synapse development in vivo, loss of NF-kappaB similarly reduces spine density and also diminishes the amplitude of synaptic responses. In contrast, after developmental synaptogenesis has plateaued, endogenous NF-kappaB activity is low and p65 deficiency no longer attenuates basal spine density. Instead, NF-kappaB in mature neurons is activated by stimuli that induce demand for new synapses, including estrogen and short-term bicuculline, and is essential for upregulating spine density in response to these stimuli. p65 is enriched in dendritic spines making local protein-protein interactions possible; however, the effects of NF-kappaB on spine density require transcription and the NF-kappaB-dependent regulation of PSD-95, a critical postsynaptic component. Collectively, our data define a distinct role for NF-kappaB in imparting transcriptional regulation required for the induction of changes to, but not maintenance of, excitatory synapse and spine density. |
