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- W4318766054 endingPage "22.2022" @default.
- W4318766054 startingPage "ENEURO.0195" @default.
- W4318766054 abstract "Temporal lobe epilepsy (TLE) is notoriously pharmacoresistant, and identifying novel therapeutic targets for controlling seizures is crucial. Long-range inhibitory neuronal nitric oxide synthase-expressing cells (LINCs), a population of hippocampal neurons, were recently identified as a unique source of widespread inhibition in CA1, able to elicit both GABAA-mediated and GABAB-mediated postsynaptic inhibition. We therefore hypothesized that LINCs could be an effective target for seizure control. LINCs were optogenetically activated for on-demand seizure intervention in the intrahippocampal kainate (KA) mouse model of chronic TLE. Unexpectedly, LINC activation at 1 month post-KA did not substantially reduce seizure duration in either male or female mice. We tested two different sets of stimulation parameters, both previously found to be effective with on-demand optogenetic approaches, but neither was successful. Quantification of LINCs following intervention revealed a substantial reduction of LINC numbers compared with saline-injected controls. We also observed a decreased number of LINCs when the site of initial insult (i.e., KA injection) was moved to the amygdala [basolateral amygdala (BLA)-KA], and correspondingly, no effect of light delivery on BLA-KA seizures. This indicates that LINCs may be a vulnerable population in TLE, regardless of the site of initial insult. To determine whether long-term circuitry changes could influence outcomes, we continued testing once a month for up to 6 months post-KA. However, at no time point did LINC activation provide meaningful seizure suppression. Altogether, our results suggest that LINCs are not a promising target for seizure inhibition in TLE." @default.
- W4318766054 created "2023-02-02" @default.
- W4318766054 creator A5011033594 @default.
- W4318766054 creator A5020856384 @default.
- W4318766054 creator A5054145718 @default.
- W4318766054 date "2023-02-01" @default.
- W4318766054 modified "2023-09-26" @default.
- W4318766054 title "LINCs Are Vulnerable to Epileptic Insult and Fail to Provide Seizure Control via On-Demand Activation" @default.
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