The MeCP2-null mouse hippocampus displays altered basal inhibitory rhythms and is prone to hyperexcitability.
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.
Division of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network, Toronto, Ontario, M5T 2S8, Canada.
Liang
L
Zhang
Jiwei
J
He
Denis G M
DG
Jugloff
James H
JH
Eubanks
D000200:Action Potentials / Q000235:genetics*; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D003344:Cortical Synchronization; D004268:DNA-Binding Proteins / Q000235:genetics; D004558:Electric Stimulation; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D053444:Inhibitory Postsynaptic Potentials / Q000235:genetics; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000378:metabolism / Q000503:physiopathology*; D009433:Neural Inhibition / Q000235:genetics*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010507:Periodicity; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000235:genetics
D004268:DNA-Binding Proteins; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D018698:Glutamic Acid