Electronic Thesis and Dissertation Repository


Master of Science




Berube, Nathalie G.

2nd Supervisor

Leung, Stan L.



The ATRX gene encodes an ATP-dependent chromatin remodeling factor and gene mutations cause developmental defects and intellectual disability. Conditional ablation of Atrx in mouse postnatal forebrain excitatory neurons (ATRX-KO) leads to spatial learning and memory impairments. Thus, we hypothesized that hippocampal synaptic transmission and plasticity are disrupted in ATRX-KO mice. Long-term potentiation (LTP), a cellular correlate of memory, and input-output relation of paired-pulse responses were studied in urethane-anesthetized mice in vivo. Theta-burst stimulation (TBS) of stratum oriens induced robust basal dendritic LTP in CA1 of both ATRX-KO and control mice, while paired-pulse facilitation (PPF) during baseline was lower in ATRX-KO mice. TBS of the medial perforant path induced CA1 distal apical dendritic LTP in control mice but was significantly decreased in ATRX-KO mice. The defects we identified in hippocampal synaptic transmission and LTP may underlie the memory impairments previously identified in the mutant mice.