4.8 Article

Decreased Subcortical Cholinergic Arousal in Focal Seizures

期刊

NEURON
卷 85, 期 3, 页码 561-572

出版社

CELL PRESS
DOI: 10.1016/j.neuron.2014.12.058

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资金

  1. NIH [R01 NS066974, R21 NS083783, P30 NS052519, F30 NS071628]
  2. Swebelius Fund
  3. Loughridge Williams Foundation
  4. Betsy and Jonathan Blattmachr Family
  5. MSTP TG [T32GM07205]

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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.

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