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.
Zhang
Liang
L
Division of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network, Toronto, Ontario, M5T 2S8, Canada.
He
Jiwei
J
Jugloff
Denis G M
DG
Eubanks
James H
JH
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