- Lost in place
- Impaired hippocampal information processing in a mouse model of intellectual disability
- Award date
- 18 May 2018
- Number of pages
- Document type
- PhD thesis
- Faculty of Science (FNWI)
- Swammerdam Institute for Life Sciences (SILS)
Certain forms of learning and long-term memory are mediated by neuronal activity in the hippocampus. For example, electrophysiological activity of hippocampal neurons recorded from rodents during exploration of an environment can reflect mapping of spatial information. These recordings can provide valuable information on impaired cognitive functioning, such as in psychiatric disease.
Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism, yet it has no effective treatment, in part because it has proven difficult to establish reliable animal models of its cognitive manifestations. Several neurophysiological and developmental hallmarks of the disease have been identified in the Fmr1-KO mouse model of FXS, which was developed to carry a mutation in same gene as the human patients.
In this thesis, we describe electrophysiological characteristics of impaired hippocampal spatial information processing in Fmr1-KO, characterizing how its neurodevelopmental phenotype affects learning and memory formation. We recorded activity from individual neurons as well as the simultaneously occurring neuronal network activity in the CA1 area of the hippocampus, while Fmr1-KO mice freely explored an environment. By contrasting these data to recordings done in healthy wild type control mice (WT), we characterize deficits in hippocampal synaptic plasticity as a result of the FXS mutation, linking its effects to an electrophysiological phenotype. Our results illustrate how affected neural coding and neuronal communication in area CA1 may contribute to the devastating cognitive symptoms of FXS, and may lead to novel approaches for potential treatment.
- Please note that the section ‘Dedication’ is not included in the thesis downloads.
Thesis (complete) (Permanent embargo)
2: Impaired hippocampal representation of place in the Fmr1-KO mouse model of fragile X syndrome (Embargo up to and including 18 May 2020)
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