Drebrin a knockout eliminates the rapid form of homeostatic synaptic plasticity at excitatory synapses of intact adult cerebral cortex

Chiye Aoki, Nobuhiko Kojima, Nicole Sabaliauskas, Lokesh Shah, Tunazzina H. Ahmed, John Oakford, Tahir Ahmed, Hiroyuki Yamazaki, Kenji Hanamura, Tomoaki Shirao

Research output: Contribution to journalArticle

Abstract

Homeostatic synaptic plasticity (HSP) is important for maintaining neurons' excitability within the dynamic range and for protecting neurons from unconstrained long-term potentiation that can cause breakdown of synapse specificity (Turrigiano [2008] Cell 135:422-435). Knowledge of the molecular mechanism underlying this phenomenon remains incomplete, especially for the rapid form of HSP. To test whether HSP in adulthood depends on an F-actin binding protein, drebrin A, mice deleted of the adult isoform of drebrin (DAKO) but retaining the embryonic isoform (drebrin E) were generated. HSP was assayed by determining whether the NR2A subunit of N-methyl-D-aspartate receptors (NMDARs) can rise rapidly within spines following the application of an NMDAR antagonist, D-APV, onto the cortical surface. Electron microscopic immunocytochemistry revealed that, as expected, the D-APV treatment of wild-type (WT) mouse cortex increased the proportion of NR2A-immunolabeled spines within 30 minutes relative to basal levels in hemispheres treated with an inactive enantiomer, L-APV. This difference was significant at the postsynaptic membrane and postsynaptic density (i.e., synaptic junction) as well as at nonsynaptic sites within spines and was not accompanied by spine size changes. In contrast, the D-APV treatment of DAKO brains did not augment NR2A labeling within the spine cytoplasm or at the synaptic junction, even though basal levels of NR2A were not significantly different from those of WT cortices. These findings indicate that drebrin A is required for the rapid (<30 minutes) form of HSP at excitatory synapses of adult cortices, whereas drebrin E is sufficient for maintaining basal NR2A levels within spines.

Original languageEnglish (US)
Pages (from-to)105-121
Number of pages17
JournalJournal of Comparative Neurology
Volume517
Issue number1
DOIs
StatePublished - 2009

Fingerprint

Neuronal Plasticity
Cerebral Cortex
Synapses
Spine
N-Methyl-D-Aspartate Receptors
Protein Isoforms
Post-Synaptic Density
Neurons
Long-Term Potentiation
drebrins
Cytoplasm
Immunohistochemistry
Electrons
Membranes
Brain
Therapeutics

Keywords

  • Drebrin A
  • Homeostatic synaptic plasticity
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Drebrin a knockout eliminates the rapid form of homeostatic synaptic plasticity at excitatory synapses of intact adult cerebral cortex. / Aoki, Chiye; Kojima, Nobuhiko; Sabaliauskas, Nicole; Shah, Lokesh; Ahmed, Tunazzina H.; Oakford, John; Ahmed, Tahir; Yamazaki, Hiroyuki; Hanamura, Kenji; Shirao, Tomoaki.

In: Journal of Comparative Neurology, Vol. 517, No. 1, 2009, p. 105-121.

Research output: Contribution to journalArticle

Aoki, C, Kojima, N, Sabaliauskas, N, Shah, L, Ahmed, TH, Oakford, J, Ahmed, T, Yamazaki, H, Hanamura, K & Shirao, T 2009, 'Drebrin a knockout eliminates the rapid form of homeostatic synaptic plasticity at excitatory synapses of intact adult cerebral cortex', Journal of Comparative Neurology, vol. 517, no. 1, pp. 105-121. https://doi.org/10.1002/cne.22137
Aoki, Chiye ; Kojima, Nobuhiko ; Sabaliauskas, Nicole ; Shah, Lokesh ; Ahmed, Tunazzina H. ; Oakford, John ; Ahmed, Tahir ; Yamazaki, Hiroyuki ; Hanamura, Kenji ; Shirao, Tomoaki. / Drebrin a knockout eliminates the rapid form of homeostatic synaptic plasticity at excitatory synapses of intact adult cerebral cortex. In: Journal of Comparative Neurology. 2009 ; Vol. 517, No. 1. pp. 105-121.
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