These authors contributed equally to the work.
Full-Length Original Research
Remodeling of dendrites and spines in the C1q knockout model of genetic epilepsy
Article first published online: 26 APR 2013
Wiley Periodicals, Inc. © 2013 International League Against Epilepsy
Volume 54, Issue 7, pages 1232–1239, July 2013
How to Cite
Ma, Y., Ramachandran, A., Ford, N., Parada, I. and Prince, D. A. (2013), Remodeling of dendrites and spines in the C1q knockout model of genetic epilepsy. Epilepsia, 54: 1232–1239. doi: 10.1111/epi.12195
- Issue published online: 1 JUL 2013
- Article first published online: 26 APR 2013
- Manuscript Accepted: 12 MAR 2013
- NINDS. Grant Number: NS012151
- NIH. Grant Number: OD010989
- American Epilepsy Society/Epilepsy Foundation of America
- Genetic epilepsy
To determine whether developmental synaptic pruning defects in epileptic C1q-knockout (KO) mice are accompanied by postsynaptic abnormalities in dendrites and/or spines.
Immunofluorescence staining was performed on biocytin-filled layer Vb pyramidal neurons in sensorimotor cortex. Basal dendritic arbors and their spines were reconstructed with NEUROLUCIDA software, and their morphologic characteristics were quantitated in Neuroexplorer.
Seven to nine completely filled pyramidal neurons were analyzed from the wild-type (WT) and C1q KO groups. Compared to WT controls, KO mice showed significant structural modifications in their basal dendrites including (1) higher density of dendritic spines (0.60 ± 0.03/μm vs. 0.49 ± 0.03/μm dendritic length in WT, p < 0.05); (2) remarkably increased occurrence of thin spines (0.26 ± 0.02/μm vs. 0.14 ± 0.02/μm dendritic length in control, p < 0.01); (3) longer dendritic length (2,680 ± 159 μm vs. 2,119 ± 108 μm in control); and (4) increased branching (22.6 ± 1.9 vs. 16.2 ± 1.3 in WT at 80 μm from soma center, p < 0.05; 12.4 ± 1.4 vs. 8.2 ± 0.6 in WT at 120 μm from soma center, respectively, p < 0.05). Dual immunolabeling demonstrated the expression of putative glutamate receptor 2 (GluR2) on some thin spines. These dendritic alterations are likely postsynaptic structural consequences of failure of synaptic pruning in the C1q KO mice.
Failure to prune excessive excitatory synapses in C1q KO mice is a likely mechanism underlying abnormalities in postsynaptic dendrites, including increased branching and alterations in spine type and density. It is also possible that seizure activity contributes to these abnormalities. These structural abnormalities, together with increased numbers of excitatory synapses, likely contribute to epileptogenesis in C1q KO mice.