Four weeks of bi-weekly treatment with 5 mg/kg KA also increased abnormal spike activity in APP/PSEN1 and not WT mice but did not impact sleep/wake behavioral states. KA treatment also impaired memory retention in the APP/PSEN1 mice in a Morris water maze task under cognitively challenging reversal learning conditions where the platform was moved to a new location. Long-term repeated low-dose KA (fourteen weeks of bi-weekly treatment with 7.5–10 mg/kg) led to high mortality in APP/PSEN1 mice. Short-term repeated low-dose KA (five daily treatments with 5 mg/kg, IP) impaired long-term potentiation in hippocampus of APP/PSEN1 but not WT mice.

We used repeated treatment with low dose kainic acid (KA) to trigger subthreshold epileptiform activity in young (less than 6 months) wild-type (WT) and APP/PSEN1 mice to test the role of disruption to the glutamatergic system in epileptiform activity changes and the development of memory deficits. Non-convulsive epileptiform activity is a common and under-studied comorbidity of Alzheimer’s disease that may significantly contribute to onset of clinical symptoms independently of other neuropathological features such as β-amyloid deposition.

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