A requirement for nuclear factor-kappaB in developmental and plasticity-associated synaptogenesis.
Matthew C H Boersma1, Erica C Dresselhaus, Lindsay M De Biase
1The Solomon H Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Summary
The p65 subunit of nuclear factor-kappa B (NF-κB) controls excitatory synapse and dendritic spine formation. NF-κB is essential for inducing changes in synapse density during development and in response to stimuli in mature neurons.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Structural plasticity of dendritic spines and synapses is crucial for neuronal circuits and information storage.
- The nuclear factor-kappa B (NF-κB) transcription factor, specifically its p65 subunit, is known to be vital for learning and memory.
Purpose of the Study:
- To investigate the role of the p65 subunit of NF-κB in the formation and morphology of excitatory synapses and dendritic spines in the hippocampus.
- To determine how NF-κB activity influences synapse development during critical periods and in response to stimuli in mature neurons.
Main Methods:
- Utilized murine hippocampal neurons for in vitro synaptogenesis studies.
- Employed in vivo synapse development models to assess the impact of NF-κB loss.
- Investigated cell-autonomous functions of NF-κB within postsynaptic neurons.
- Examined NF-κB activation by specific stimuli like estrogen and bicuculline.
Main Results:
- Loss of endogenous p65 decreased dendritic spine density and spine head volume during synaptogenesis.
- NF-κB deficiency reduced spine density and synaptic response amplitude during in vivo synapse development.
- In mature neurons, NF-κB was activated by stimuli demanding new synapses and was essential for upregulating spine density.
- NF-κB's effect on spine density requires transcription and regulation of PSD-95.
Conclusions:
- NF-κB, via its p65 subunit, plays a critical role in regulating excitatory synapse and dendritic spine density during development.
- NF-κB is essential for inducing synapse density changes in response to specific stimuli in mature neurons.
- The study defines a role for NF-κB in the transcriptional regulation required for the induction, but not maintenance, of excitatory synapse and spine density.
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