Abstracts

Rationale: Mitochondrial dysfunction is associated with cognitive impairment and there is increasing interest in mitochondria as therapeutic targets for preventing and treating neurological disorders. Temporal lobe epilepsy (TLE) is the most common type of drug resistant epilepsy and is often comorbid with substantial cognitive impairment. Oxidative stress and reduced mitochondrial respiratory chain complex I (MRCI) function has been found in human resected brain tissue. The Kv1.1 knockout (KO) mouse preclinical model of TLE displays cognitive deficits, reduced hippocampal synaptic plasticity and altered network oscillations involved in memory consolidation (i.e., sharp waves and high frequency oscillations; SPW-HFOs). Moreover, similar to human TLE, KO hippocampal mitochondria have reduced MRCI function which is due to inhibition by reactive oxygen species (ROS). Thus, we hypothesize that excessive mitochondrial ROS contributes to impaired synaptic and network correlates of memory in KO hippocampus.

Methods: Ventral hippocampal slices from wildtype (WT) and KO mice were placed on a planar multielectrode array (MED64, Alpha Med Systems, Osaka, Japan). Schaffer collaterals were stimulated, and postsynaptic extracellular field potentials were recorded in CA1 stratum radiatum. Paired stimulations (40 ms inter-stimulus interval) and a high frequency burst (HFB) stimulation (8 trains containing 8 bursts at 200 Hz for 40 ms, with an inter-burst interval of 2 s) were used to elicit paired pulse facilitation and long-term potentiation, (LTP). Gap free recordings were used to monitor spontaneous field potentials. Stable baseline recordings were achieved before perfusion of MitoQ (500 nM). Mitochondrial superoxide was assessed using MitoSox Red. A two-way ANOVA with Tukey’s post-hoc test was used with p< 0.05 considered significant.