A Role for the NMDA receptor in synaptic plasticity in the hippocampus of the Fmr1 transgenic mouse model of Fragile X Syndrome

dc.contributor.authorBostrom, Crystal A.
dc.contributor.supervisorChristie, Brian R.
dc.date.accessioned2012-07-23T15:19:07Z
dc.date.available2012-07-23T15:19:07Z
dc.date.copyright2012en_US
dc.date.issued2012-07-23
dc.degree.departmentDept. of Biologyen_US
dc.degree.levelMaster of Science M.Sc.en_US
dc.description.abstractFragile-X syndrome (FXS) is the most common form of inherited intellectual impairment. Caused by the transcriptional repression of the Fmr1 gene on the X chromosome, FXS results in the loss of the Fragile-X Mental Retardation Protein (FMRP). Human female patients with FXS are heterozygous for the Fmr1 mutation whereas males are hemizygous. FXS has been studied far less in females than in males due to a generally less severe clinical phenotype. Previous research has implicated the metabotropic glutamate receptor (mGluR) in synaptic plasticity alterations in the cornu ammonis area 1 (CA1) region of the juvenile male Fmr1 knock-out (KO) hippocampus. In contrast, our investigations into the young adult dentate gyrus (DG) subfield of the hippocampus have revealed N-methyl-D-aspartate receptor (NMDAR)-associated impairments in synaptic plasticity. The current study sought to extend these investigations to the young adult female Fmr1 heterozygous (Het) and Fmr1 KO mouse as well as investigate NMDAR- and mGluR-mediated long-term depression (LTD) in the DG and CA1 of the young adult male Fmr1 KO mouse. Input-output curves and paired pulse measures of short-term plasticity were also evaluated in all genotypes. Field electrophysiology revealed a significant impairment in long-term potentiation (LTP) and LTD in male Fmr1 KO and female Fmr1 Het mice that was associated with NMDAR alteration. A more robust synaptic protocol was not able to rescue LTP in the male Fmr1 KO DG. Paired-pulse low-frequency stimulation and (RS)-3,5-dihydroxyphenylglycine (DHPG)-induced mGluR-LTD was intact in all genotypes and brain regions examined. Although further investigation will be required to expand our understanding of FXS and to fully elucidate the mechanisms behind intact synaptic plasticity in the female Fmr1 KO mouse, our results suggest that NMDARs may be poised as important contributors to hippocampal pathophysiology in FXS.en_US
dc.description.scholarlevelGraduateen_US
dc.identifier.urihttp://hdl.handle.net/1828/4073
dc.language.isoenen_US
dc.rights.tempAvailable to the World Wide Weben_US
dc.subjectelectrophysiologyen_US
dc.subjectFmr1en_US
dc.subjectFragile X Syndromeen_US
dc.subjectmGluRen_US
dc.subjectmurineen_US
dc.subjecthippocampusen_US
dc.subjectdentate gyrusen_US
dc.subjectCA1en_US
dc.subjectNMDARen_US
dc.titleA Role for the NMDA receptor in synaptic plasticity in the hippocampus of the Fmr1 transgenic mouse model of Fragile X Syndromeen_US
dc.typeThesisen_US

Files

Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Bostrom_Crystal_MSc_2012.pdf
Size:
1.14 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.74 KB
Format:
Item-specific license agreed upon to submission
Description: