On April 29th, a paper of Dr. Fengfei Ding from Tongji Hospital, Huazhong University of Science and Technology and her collaborators, was published on Science titled Changes in the Composition of Brain Interstitial Ions Control the Sleep-wake Cycle. They have proved that changes in extracellular ions can cause sleep/wake-dependent changes in neuronal activity.

The research shows that the changes in extracellular ions can not only play a critical role in neural activity, but also trigger shrinkage of extracellular space volume, which is conducive to metabolism. In their theory, brain was aroused by the concerted release of neuromodulators—including norepinephrine, acetylcholine, histamine, dopamine, and orexin, which are released by neurons located in the brainstem, hypothalamus, and basal forebrain. These signals activate the cortex and the abilities of learning and memory. However, the theory can’t explain the instant activation of billions of neurons, which is the necessity of wakefulness. Neither can it be applied to explain the mechanism of maintaining awake and sleep states.

The research shows that the concentration of extracellular ions controls the sleep/wake-dependent changes. As a matter of fact, the researchers can control the sleep/wake-dependent changes by altering the concentration of [K+]e, [Ca2+]e, [Mg2+]e, and [H+]e without neuromodulators. They believe that [K+]e is crucial as they detect state-dependent [K+]e shifts in the transition of excitatory activity.

Changes in extracellular ions may thus be a cause, rather than consequences, of sleep/wake-dependent changes in neuron-activity.

The intercellular movements of positive ions relieve polarization and depolarization block of neurons, causing long-term potentiation. It is predicted that changes in the composition of brain interstitial ions may also be a cause for fatigue and loss of memory of insomnia.

By the study of controlling sleep-wake cycle, their observations add new and critical insight into understanding of the loss of consciousness during sleep and anesthesia and facilitate the development of new sleeping pills.