Journal article
Impaired Serotonergic Brainstem Function during and after Seizures
The Journal of neuroscience, Vol.36(9), pp.2711-2722
03/02/2016
DOI: 10.1523/JNEUROSCI.4331-15.2016
PMCID: PMC4879214
PMID: 26937010
Abstract
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.
Seizures often cause impaired breathing, cardiac dysfunction, and loss of consciousness. The brainstem and, specifically, brainstem serotonin neurons are thought to play an important role in controlling breathing, cardiac function, and arousal. We used an established rat seizure model to study the overall neuronal activity in the brainstem as well as firing of specific serotonin neurons while measuring cardiorespiratory function. Our results demonstrated overall decreases in brainstem neuronal activity and marked downregulation of lower brainstem serotonin neuronal firing in association with decreased breathing and heart rate during and after seizures. These findings point the way toward new treatments to augment brainstem function and serotonin, aiming to prevent seizure complications and reduce morbidity and mortality in people living with epilepsy.
Details
- Title: Subtitle
- Impaired Serotonergic Brainstem Function during and after Seizures
- Creators
- Qiong Zhan - Departments of Neurology, Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China, Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, ChinaGordon F Buchanan - Departments of NeurologyJoshua E Motelow - Departments of NeurologyJohn Andrews - Departments of NeurologyPetr Vitkovskiy - Departments of NeurologyWilliam C Chen - Departments of NeurologyFlorian Serout - Departments of NeurologyAbhijeet Gummadavelli - Departments of NeurologyAdam Kundishora - Departments of NeurologyMoran Furman - Departments of NeurologyWei Li - Departments of Neurology, Department of Neurosurgery, Jinling Hospital, School of Medicine Nanjing University, Nanjing Jiangsu 210002, China, andXiao Bo - Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaGeorge B Richerson - Departments of Neurology and Molecular Physiology and Biophysics, and Veterans Affairs Medical Center, Iowa City, Iowa 52246Hal Blumenfeld - Departments of Neurology, Neuroscience, and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520, hal.blumenfeld@yale.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.36(9), pp.2711-2722
- Publisher
- United States
- DOI
- 10.1523/JNEUROSCI.4331-15.2016
- PMID
- 26937010
- PMCID
- PMC4879214
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Grant note
- R01 NS066974 / NINDS NIH HHS U54 NS041069 / NINDS NIH HHS P20 NS076916 / NINDS NIH HHS R01 NS096088 / NINDS NIH HHS R21 NS083783 / NINDS NIH HHS T32GM07205 / NIGMS NIH HHS U54NS041069 / NINDS NIH HHS P30 NS052519 / NINDS NIH HHS T32 GM007205 / NIGMS NIH HHS U01 NS090414 / NINDS NIH HHS
- Language
- English
- Date published
- 03/02/2016
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984020502302771
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