Abstract
Sevoflurane can induce memory impairment during clinical anesthesia; however, the underlying mechanisms are largely unknown. TASK-3 channels are one of the potential targets of sevoflurane. Accumulating evidence supports a negative role of intracranial theta rhythms (4–12 Hz) in memory formation. Here, we investigated whether TASK-3 channels contribute to sevoflurane-induced memory impairment by regulating hippocampal theta rhythms. In this study, the memory performance of mice was tested by contextual fear conditioning and inhibitory avoidance experiments. The hippocampal local field potentials (LFPs) were recorded from chronically implanted electrodes located in CA3 region. The results showed that sevoflurane concentration-dependently impaired the memory function of mice, as evidenced by the decreased time mice spent on freezing and reduced latencies for mice to enter the shock compartment. Our electrophysiological results revealed that sevoflurane also enhanced the spectral power of hippocampal LFPs (1–30 Hz), particularly in memory-related theta rhythms (4–12 Hz). These effects were mitigated by viral-mediated knockdown of TASK-3 channels in the hippocampal CA3 region. The knockdown of hippocampal TASK-3 channels significantly reduced the enhancing effect of sevoflurane on hippocampal theta rhythms and alleviated sevoflurane-induced memory impairment. Our data indicate that sevoflurane can increase hippocampal theta oscillations and impair memory function via TASK-3 channels.
Highlights
Sevoflurane is a commonly used inhaled anesthetic in clinics
By analyzing the targets of sevoflurane and proteins related to the regulation of theta rhythms, we found that TWIK-related acid-sensitive K+ channel 3 (TASK-3) channels may be a potential target for sevoflurane to regulate theta rhythms
We investigated the effect of different concentrations of sevoflurane (0.1, 0.2, 0.3 × loss of righting reflex (LORR) EC50) on memory by using a contextual fear conditioning experiment (Figure 1B)
Summary
Sevoflurane is a commonly used inhaled anesthetic in clinics. Sevoflurane can induce temporary memory impairment to prevent intraoperative awareness during anesthesia. The memorydamaging effect of sevoflurane has been widely confirmed. A functional magnetic resonance imaging (fMRI) study revealed that sevoflurane at subanesthetic concentration (0.25× minimum alveolar concentration) preferentially affected memory-related regions, such as the visual cortices, thalamus and hippocampus (Ramani et al, 2007). Clinical studies have shown that sevoflurane at approximately 0.25% inhibits human emotional memory (Alkire et al, 2008). Memory is thought to be represented by a set of distributed neurons that are concurrently activated, and brain rhythms are thought to play a key role in memory formation by synchronizing and coordinating the activities of distributed neurons during memory operations (Colgin, 2016).
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