The Brain and Narcolepsy

Narcolepsy is a disorder that affects humans and other species by interfering with the neural mechanisms that normally control the different features of sleep and arousal. People and animals who suffer from this disorder experience excessive sleepiness during the day and are troubled by the intrusion of REM sleep features into their wakeful state. In addition, they sleep in fits and bursts, and typically do not experience non-REM sleep before the REM stage when they fall asleep.

Usually during sleep, certain brain and spinal cord circuits, which are controlled by naturally occurring chemicals, inhibit bodily movement by blocking the neural excitation of our muscles and thus, in essence, paralyze us. This happens to prevent us from acting out our dreams or moving according to their dictates whilst we are asleep. The main symptom of narcolepsy – cataplexy – is caused by the degeneration of a certain part of these particular circuits, such that muscle tone is lost even during wakeful states. Jerome Siegel, a sleep researcher at the University of California, Los Angeles, illustrates this phenomenon well with the following diagram and explanation:

neural circuitry

The degeneration of cells in the forebrain eliminates inhibitory signals that are important for regulating the activity of cells in the amygdala, a structure involved in emotional responses. The loss of the inhibitory signals in the amygdala causes increased activity in amygdala connections (light blue) to the pons, in turn pressing a cellular "brake" (red) that reduces activity in the locus coeruleus (green). This removes a source of excitation from neurons (orange) that control muscles. The cell loss in the amygdala also indirectly activates two circuits (pink and dark blue) in the pons that stimulate nerves in two areas of the medial medulla (yellow) that actively inhibit motor neurons. The result of the simultaneous loss of excitation and onset of inhibition in the motor neurons is a loss of muscle tone, causing the narcoleptic to fall.

Watch a video (avi format, best viewed with Windows Media Player) of a cataplectic attack in a human adult male. (This video is courtesy the Center of Narcolepsy at the Stanford School of Medicine.)

Siegel also talks about the neurotransmitter Hypocretin (purple) that is secreted by the hypothalamus, and that acts extensively on these circuits, but we cover that separately in our explanation of the hypocretin model.

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