Synaptic circuit abnormalities of motor-frontal layer 2/3 pyramidal neurons in a mutant mouse model of Rett syndrome
Section snippets
MeCP2−/y mice
Male wild type (WT) and hemizygous MeCP2−/y littermates were obtained from colonies of heterozygous mutant females and WT males (MeCP2tm1.1Bird, Jackson Laboratories) (Guy et al., 2001). Experiments involving MeCP2−/y mice were performed with the experimenter blind to genotype. Tail samples were collected at the time of recordings, and genotyped according to the vendor's PCR protocol (http://jaxmice.jax.org). Primers were MeCP2-common (5′-ggT AAA gAC CCA TgT gAC CC-3), MeCP2 wild type (5′-ggC
Reduced cortical thickness in MeCP2−/y mice
We prepared brain slices from 3 to 4 week old mice, using an off-sagittal angle to obtain slices with M1 and adjacent somatosensory (S1) cortex (Weiler et al., 2008) (Figs. 1 A, B). M1 was identified as agranular cortex anterior to somatosensory ‘barrel’ cortex. Because cortical thickness has been shown to be reduced in older MeCP2-null mice (Fukuda et al., 2005, Kishi and Macklis, 2004), we examined M1 cortical thickness in these slices prepared from WT (Fig. 1A) and mutant (Fig. 1B) mice.
Discussion
In this study we examined neocortical synaptic circuits in presymptomatic hemizygous male MeCP2tm1.1Bird mice (“Bird” strain, in which exons 3 and 4 of the MeCP2 gene are deleted), a model of RTT (Guy et al., 2001). We used LSPS to map local sources of excitatory input to L2/3 pyramidal neurons in the motor-frontal area of WT and MeCP2−/y mice. We observed a reduction in excitatory synaptic input, extending previous observations of generally decreased excitation onto cortical neurons (Chao et
Acknowledgments
We thank M. Bevan, A. Contractor, M. Hooks, G. Maccaferri, and M. Tresch for valuable input. We are especially grateful to N. Weiler for experimental efforts in the early stages of this work and for comments on earlier drafts. We thank M. Hooks for statistical advice and comments on a draft. Support: Simons Foundation, Rett Syndrome Research Foundation (International Rett Syndrome Foundation), and National Institutes of Health (NS061534 to LW; NS061963 to GS).
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