Long-lasting
confusion and memory difficulties during the postictal state remain a major unmet problem in
epilepsy that lacks pathophysiological explanation and treatment. We previously identified that long-lasting periods of severe postictal hypoperfusion/
hypoxia, not
seizures per se, are associated with memory impairment after temporal lobe
seizures. While this observation suggests a key pathophysiological role for insufficient energy delivery, it is unclear how the networks that underlie episodic memory respond to vascular constraints that ultimately give rise to
amnesia. Here, we focused on cellular/network level analyses in the CA1 of hippocampus in vivo to determine if neural activity, network oscillations, synaptic transmission, and/or synaptic plasticity are impaired following kindled
seizures. Importantly, the induction of severe postictal hypoperfusion/
hypoxia was prevented in animals treated by a
COX-2 inhibitor, which experimentally separated
seizures from their vascular consequences. We observed complete activation of CA1 pyramidal neurons during brief
seizures, followed by a short period of reduced activity and flattening of the local field potential that resolved within minutes. During the postictal state, constituting
tens of minutes to hours, we observed no changes in neural activity, network oscillations, and synaptic transmission. However, long-term potentiation of the temporoammonic pathway to CA1 was impaired in the postictal period, but only when severe local
hypoxia occurred. Lastly, we tested the ability of rats to perform object-context discrimination, which has been proposed to require temporoammonic input to differentiate between sensory experience and the stored representation of the expected object-context pairing. Deficits in this task following
seizures were reversed by COX-2 inhibition, which prevented severe postictal
hypoxia. These results support a key role for hypoperfusion/
hypoxia in postictal memory impairments and identify that many aspects of hippocampal network function are resilient during severe
hypoxia except for long-term synaptic plasticity.