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H. LIN, S. ZHONG, A. GHAVAMI, S. BENT, L. MRZLJAK, V. BEAUMONT, G. TOMBAUGH

Huntington’s disease (HD) is a lethal autosomal dominant neurodegenerative disease that leads to deficits in motor control and cognitive/memory functions. Electrophysiological studies of the R6/2 mouse model of HD, in-vitro, have shown impairments in long-term potentiation (LTP) and paired-pulse responses in hippocampal pathways. The hippocampus is an essential brain structure for episodic/spatial memory processing and impairment may contribute to cognitive dysfunction in HD. Here we recorded field excitatory post-synaptic potentials (fEPSP) in urethane-anesthetized R6/2 and WT mice (~8 weeks old) in the stratum radiatum layer of CA1 following contralateral stimulation of CA3 to investigate hippocampal function in-vivo. fEPSP responses were recorded at different stimulus intensities to generate input/output (IO) curves. R6/2 mice showed left-shifted (more excitable) IO curves relative to those in WT littermates. There were occurrences of putative dendritic spikes in the fEPSP waveforms with increasing stimulus intensities for both genotypes; however, dendritic spike appearance was more frequently observed in R6/2 mice at comparable stimulus intensities to WT mice. This is suggestive of dendritic hyper-excitability that could lead to a lower threshold for seizure activity. In summary, we report abnormal hippocampal activity characterized by an increase in CA1 excitability in the R6/2 mouse model of HD, which may contribute to impaired cognitive function and the increased susceptibility of R6/2 mice to epileptic seizure activity.