Master of Science
Berube, Nathalie G.
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.
Gugustea, Radu, "Effect of ATRX Inactivation on Hippocampal Synaptic Plasticity in Mice" (2019). Electronic Thesis and Dissertation Repository. 6118.