{"id":1710,"date":"2011-04-06T00:00:12","date_gmt":"2011-04-06T00:00:12","guid":{"rendered":"http:\/\/bergleslab.com\/wordpress\/?p=1710"},"modified":"2017-10-18T19:37:24","modified_gmt":"2017-10-18T19:37:24","slug":"boersma-2011","status":"publish","type":"post","link":"http:\/\/bergleslab.com\/index.php\/2011\/04\/06\/boersma-2011\/","title":{"rendered":"A requirement for nuclear factor-kappaB in developmental and plasticity-associated synaptogenesis."},"content":{"rendered":"
J Neurosci.<\/a> 2011 Apr 6;31(14):5414-25. doi: 10.1523\/JNEUROSCI.2456-10.2011.<\/div>\n

A requirement for nuclear factor-kappaB in developmental and plasticity-associated synaptogenesis.<\/h4>\n
Boersma MC<\/a>, Dresselhaus EC<\/a>, De Biase LM<\/a>, Mihalas AB<\/a>, Bergles DE<\/a>, Meffert MK<\/a>.<\/div>\n
<\/div>\n
\n <\/p>\n

<\/h4>\n

Abstract<\/h4>\n
\n

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-\u03baB (NF-\u03baB) transcription factor, which is required for learning and memory, controls excitatory synapse and dendritic spine formation and morphology in murine hippocampal neurons. Endogenous NF-\u03baB activity is elevated by excitatory transmission during periods of rapid spine and synapse development. During in vitro synaptogenesis, NF-\u03baB enhances dendritic spine and excitatory synapse density and loss of endogenous p65 decreases spine density and spine head volume. Cell-autonomous function of NF-\u03baB within the postsynaptic neuron is sufficient to regulate the formation of both presynaptic and postsynaptic elements. During synapse development in vivo, loss of NF-\u03baB similarly reduces spine density and also diminishes the amplitude of synaptic responses. In contrast, after developmental synaptogenesis has plateaued, endogenous NF-\u03baB activity is low and p65 deficiency no longer attenuates basal spine density. Instead, NF-\u03baB 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-\u03baB on spine density require transcription and the NF-\u03baB-dependent regulation of PSD-95, a critical postsynaptic component. Collectively, our data define a distinct role for NF-\u03baB in imparting transcriptional regulation required for the induction of changes to, but not maintenance of, excitatory synapse and spine density.<\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

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-\u03baB (NF-\u03baB) transcription factor, which is required for learning and memory, controls excitatory synapse and dendritic spine formation and morphology in murine hippocampal neurons. Endogenous NF-\u03baB activity is elevated by excitatory transmission during periods of rapid spine and synapse development. During in vitro synaptogenesis, NF-\u03baB enhances dendritic spine and excitatory synapse density and loss of endogenous p65 decreases spine density and spine head volume. Cell-autonomous function of NF-\u03baB within the postsynaptic neuron is sufficient to regulate the formation of both presynaptic and postsynaptic elements. During synapse development in vivo, loss of NF-\u03baB similarly reduces spine density and also diminishes the amplitude of synaptic responses. In contrast, after developmental synaptogenesis has plateaued, endogenous NF-\u03baB activity is low and p65 deficiency no longer attenuates basal spine density. Instead, NF-\u03baB 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-\u03baB on spine density require transcription and the NF-\u03baB-dependent regulation of PSD-95, a critical postsynaptic component. Collectively, our data define a distinct role for NF-\u03baB in imparting transcriptional regulation required for the induction of changes to, but not maintenance of, excitatory synapse and spine density.<\/p>\n","protected":false},"author":1,"featured_media":1987,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[78,33],"tags":[92],"class_list":["post-1710","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-original-research","category-publications","tag-synaptogensis"],"_links":{"self":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/1710","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/comments?post=1710"}],"version-history":[{"count":3,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/1710\/revisions"}],"predecessor-version":[{"id":2111,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/1710\/revisions\/2111"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/media\/1987"}],"wp:attachment":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/media?parent=1710"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/categories?post=1710"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/tags?post=1710"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}