Early synaptic hippocampal deficits in the Q175FDN mouse model of Huntington Disease

Ravalia, Adam Shahim (2019) Early synaptic hippocampal deficits in the Q175FDN mouse model of Huntington Disease. Masters thesis, Memorial University of Newfoundland.

[English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (3MB)

Abstract

Huntington Disease (HD) is an inherited neurodegenerative disease caused by a CAG repeat expansion in the gene encoding the huntingtin protein. The resultant mutant huntingtin triggers numerous and severe neuronal abnormalities. Although motor deficits manifest during midlife, subtle cognitive aberrations can be detected prior to the onset of an overt behavioural phenotype. However, knowledge surrounding the cognitive deficits in the early stages of HD is scarce. Here, we studied hippocampal synaptic properties, including activity-dependent plasticity and nanoscale architecture in a mouse model of HD prior to the onset of motor symptoms. We focused on the hippocampus due to its involvement in cognitive function and the debilitating cognitive symptoms described by HD patients. Multi-electrode array recordings of synaptic activities revealed impairments in plasticity, while super-resolution microscopy elucidated clear alterations in synaptic nanoarchitecture of the hippocampus. Our data demonstrate detrimental effects of mHtt expression on hippocampal structure and function in presymptomatic HD.

Actions (login required)

View Item