The MeCP2-null mouse hippocampus displays altered basal inhibitory rhythms and is prone to hyperexcitability
Version of Record online: 30 NOV 2007
Copyright © 2007 Wiley-Liss, Inc.
Volume 18, Issue 3, pages 294–309, March 2008
How to Cite
Zhang, L., He, J., Jugloff, D. G. M. and Eubanks, J. H. (2008), The MeCP2-null mouse hippocampus displays altered basal inhibitory rhythms and is prone to hyperexcitability. Hippocampus, 18: 294–309. doi: 10.1002/hipo.20389
- Issue online: 21 FEB 2008
- Version of Record online: 30 NOV 2007
- Manuscript Accepted: 22 OCT 2007
- Canadian Institutes of Health Research. Grant Numbers: MOP-57765, MOP-81104
- Rett syndrome;
- Methyl DNA-binding factor;
- brain oscillations;
- neuronal synchrony
Rett syndrome is an autism-spectrum disorder caused by loss of function mutations within the gene encoding methyl CpG-binding protein 2 (MeCP2). While subtle decreases in synaptic plasticity have been detected within cortical and hippocampal neurons of Mecp2-null mice, only minimal information exists regarding how the loss of MeCP2 affects network activity in the brain. To address this issue, we compared the intrinsic network activities of Mecp2-null hippocampal slices derived from symptomatic mice to wild-type slices. Extracellular and whole-cell patch recordings revealed that although spontaneous, IPSP-based rhythmic activity is present in Mecp2-null slices; its frequency is significantly reduced from wild-type. This reduction was not associated with alterations in the gross electrophysiological properties of hippocampal neurons, but was associated with a decreased level of spontaneous glutamate receptor-mediated synaptic currents in hippocampal CA3 neurons. Paradoxically, however, repetitive sharp wave-like discharges were readily induced in the Mecp2-null hippocampal slices by a brief train of high-frequency stimulation commonly used to establish long-term potentiation at wild-type slices. Taken together, our data indicate that the Mecp2-null hippocampal CA3 circuit has diminished basal inhibitory rhythmic activity, which in turn renders the circuitry prone to hyperexcitability. © 2007 Wiley-Liss, Inc.