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Brain Stimul. 2015 Jan-Feb;8(1):36-41. doi: 10.1016/j.brs.2014.09.003. Epub 2014 Sep 16.

Cortical network switching: possible role of the lateral septum and cholinergic arousal.

Author information

1
Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
2
Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
3
Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
4
Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: hal.blumenfeld@yale.edu.

Abstract

BACKGROUND:

Cortical networks undergo large-scale switching between states of increased or decreased activity in normal sleep and cognition as well as in pathological conditions such as epilepsy. We previously found that focal hippocampal seizures in rats induce increased neuronal firing and cerebral blood flow in subcortical structures including the lateral septal area, along with frontal cortical slow oscillations resembling slow wave sleep. In addition, stimulation of the lateral septum in the absence of a seizure resulted in cortical deactivation with slow oscillations.

HYPOTHESIS:

We hypothesized that lateral septal activation might cause neocortical deactivation indirectly, possibly through impaired subcortical arousal. But how does subcortical stimulation cause slow wave activity in frontal cortex? How do arousal neurotransmitter levels (e.g. acetylcholine) change in cortex during the excitation of inhibitory projection nuclei?

METHODS AND RESULTS:

In the current study, we used simultaneous electrophysiology and enzyme-based amperometry in a rat model, and found a decrease in choline, along with slow wave activity in orbital frontal cortex during lateral septal stimulation in the absence of seizures. In contrast, the choline signal and local field potential in frontal cortex had no significant changes when stimulating the hippocampus, but showed increased choline and decreased slow wave activity with an arousal stimulus produced by toe pinch.

CONCLUSIONS:

These findings indicate that the activation of subcortical inhibitory structures (such as lateral septum) can depress subcortical cholinergic arousal. This mechanism may play an important role in large-scale transitions of cortical activity in focal seizures, as well as in normal cortical function.

KEYWORDS:

Acetylcholine; Consciousness; Deactivation; Default mode network; Lateral septum; Slow oscillations

PMID:
25440289
PMCID:
PMC4277718
DOI:
10.1016/j.brs.2014.09.003
[Indexed for MEDLINE]
Free PMC Article

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