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.

Recent findings in narcoleptic dogs suggest that mutations in receptors for a neurotransmitter called hypocretin/orexin in the lateral hypothalamus can also cause cataplexy and the other symptoms of narcolepsy. The mutations may act by removing excitatory inputs (violet) to cells that maintain muscle tone and arousal and by triggering the degeneration seen in the forebrain.--J.M.S.