期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 9, 页码 2711-2722出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4331-15.2016
关键词
brainstem; consciousness; respiratory; serotonin; SUDEP; temporal lobe epilepsy
资金
- National Institutes of Health [R01 NS066974, R21 NS083783, P30 NS052519, P20 NS076916, U54NS041069, MSTP TG T32GM07205]
- VA Medical Center
- Epilepsy Foundation (Postdoctoral Research and Training Award)
- China Scholarship Council (Postgraduate Scholarship Program) [CSC 201206370075]
- Howard Hughes Medical Institute (Citizens United for Research against Epilepsy Medical Student Fellowship)
- Loughridge Williams Foundation
- Betsy and Jonathan Blattmachr family
Impaired breathing, cardiac function, and arousal during and after seizures are important causes of morbidity and mortality. Previous work suggests that these changes are associated with depressed brainstem function in the ictal and post-ictal periods. Lower brainstem serotonergic systems are postulated to play an important role in cardiorespiratory changes during and after seizures, whereas upper brainstem serotonergic and other systems regulate arousal. However, direct demonstration of seizure-associated neuronal activity changes in brainstem serotonergic regions has been lacking. Here, we performed multiunit and single-unit recordings from medullary raphe and midbrain dorsal raphe nuclei in an established rat seizure model while measuring changes in breathing rate and depth as well as heart rate. Serotonergic neurons were identified by immunohistochemistry. Respiratory rate, tidal volume, and minute ventilation were all significantly decreased during and after seizures in this model. We found that population firing of neurons in the medullary and midbrain raphe on multiunit recordings was significantly decreased during the ictal and post-ictal periods. Single-unit recordings from identified serotonergic neurons in the medullary raphe revealed highly consistently decreased firing during and after seizures. In contrast, firing of midbrain raphe serotonergic neurons was more variable, with a mixture of increases and decreases. The markedly suppressed firing of medullary serotonergic neurons supports their possible role in simultaneously impaired cardiorespiratory function in seizures. Decreased arousal likely arises from depressed population activity of several neuronal pools in the upper brainstem and forebrain. These findings have important implications for preventing morbidity and mortality in people living with epilepsy.
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