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by Barbara E. Jones, PhD

I seek to understand how the brain generates waking and sleeping. My research group studies the chemical neurotransmitters, neuroanatomical projections and electrophysiology of the specific neurons that generate waking and those neurons which reciprocally suppress waking and generate sleep. The sleep-waking cycle is actually composed of three distinct states: waking, slow wave sleep (SWS), when the brain is resting, and rapid eye movement sleep (REMS) when the brain is dreaming. To study the neural systems producing these states, we use immunohistochemical and neuroanatomical staining combined with electrophysiological recording of neurons in rats.

With my colleagues, I have shown that certain neurons in the basal forebrain release acetylcholine (ACh) into the cerebral cortex and thereby stimulate fast cortical activity, as evident on the electroencephalogram (EEG). By recording from these particular cholinergic neurons, we found that they fire during waking and REMS, when fast EEG activity is present along with heightened cortical processing of either waking or dreaming. The ACh released from these neurons excites the cortical neurons in part through receptors that are also stimulated by nicotine, one of the major stimulants used by man. We have identified other neurons in the basal forebrain which release GABA, the major inhibitory neurotransmitter in the brain. Some of these neurons fire during SWS, when slow EEG activity is present along with a loss of consciousness. The GABA released from these neurons can inhibit the cholinergic neurons to arrest cortical fast activity and elicit cortical slow wave activity. GABA acts upon receptors which are targeted by the major hypnotic drugs used to treat insomnia.

We have also been able to elucidate the way in which particular neurons in the hypothalamus promote waking and prevent sleep. These neurons release a peptide called orexin (or hypocretin), which has been found to be essential for the maintenance of waking, since in its absence, narcolepsy with cataplexy occurs in humans and animals, including dogs and horses. Our work has revealed that the orexin neurons fire to release orexin during behavioral arousal and thus stimulate other key arousal systems and the cerebral cortex to promote waking with muscle tone and cortical activation. In absence of these neurons and their chemical in human cases of narcolepsy, individuals can pass directly from an active waking state and particularly a mirthful emotional state, into a cataplectic state with loss of muscle tone, paralysis, loss of conscious awareness and passage into sleep with dreaming.

Barbara Jones, Professor in the Department of Neurology and Neurosurgery, was recruited to The Neuro from the University of Chicago in 1977. She has been invited by colleagues three times to spend a year as Visiting Professor at the University of Geneva. In 2010, Dr. Jones was named Distinguished Scientist by the Sleep Research Society, and was elected a Fellow of the Royal Society of Canada.