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Neuron. 2015 Feb 4;85(3):561-72. doi: 10.1016/j.neuron.2014.12.058.

Decreased subcortical cholinergic arousal in focal seizures.

Author information

1
Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA.
2
Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, Jiangsu Province, People's Republic of China.
3
Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
4
Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
5
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
6
Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA; Core Center for Quantitative Neuroscience with Magnetic Resonance (QNMR), Yale University School of Medicine, New Haven, CT 06520, USA.
7
Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA; Core Center for Quantitative Neuroscience with Magnetic Resonance (QNMR), Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: hal.blumenfeld@yale.edu.

Abstract

Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function, including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a critical mechanism for loss of consciousness in focal temporal lobe seizures.

PMID:
25654258
PMCID:
PMC4319118
DOI:
10.1016/j.neuron.2014.12.058
[Indexed for MEDLINE]
Free PMC Article
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