PT  - JOURNAL ARTICLE
AU  - Julia Chartove
AU  - Wenlin Liao
AU  - Aniqa Hassan
AU  - Mary McMullen
AU  - Rachel White
AU  - Sangwon Kim
AU  - Gregory C. Carlson
TI  - Hippocampal circuit abnormalities in MeCP2+/− mouse model of Rett syndrome
AID  - 10.1101/034835
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 034835
4099  - http://biorxiv.org/content/early/2015/12/18/034835.short
4100  - http://biorxiv.org/content/early/2015/12/18/034835.full
AB  - Rett syndrome (RTT) has a complex developmental course over childhood and adolescence. Patients with RTT often have a pre-symptomatic period with no or little outward signs of the disorder, followed by developmental arrest and regression. Following regression, the individual’s condition is not static, as they often progress into defined stages with unique neurological symptoms. Similarly, the progression of RTT-like symptoms in female mice heterozygous for a null-mutation has a prodromal and symptomatic period. Change in functional local circuit connectivity was studied using hippocampal slices, assaying Schaffer evoked activity in area CA1 using fast voltage sensitive dye imaging. With this technique the local functional interactions between the excitatory and inhibitory components of the circuit can be characterized. The prodromal period was associated with a shift in extent of excitation into the stratum oriens of the hippocampus and reduced sensitivity to changes in divalent cation concentration. These data suggest that hyperexcitability of the hippocampus at the circuit level may contribute to the prodromal reduction in cognitive performance and the onset of developmental regression.