This issue of Sleep Science contains two excellent

This issue of Sleep Science contains two excellent review articles by Garcia-Rill and his colleagues examining the role of reticular activating system, especially the pedunculopontine (PPT) nucleus, in the pathophysiology of insomnia, schizophrenia, and other neuropsychiatric disorders . The PPT nucleus is one of the major aggregations of cholinergic neurons in the mammalian brainstem capable of synthesizing acetylcholine, but also other neurotransmitters and peptides . In addition, PPT cholinergic vegf tyrosine kinase inhibitor also synthesize a gaseous neuromodulator, nitric oxide. Interestingly, cells in the PPT are involved in regulation of both wakefulness and REM sleep . About 10 years ago, the Garcia-Rill lab reported for the first time the presence of electrical coupling through gap junctions of some cells in each of three major elements of the arousal system, including the PPT . This discovery helped explain how gap junction blockers like halothane and propofol can put us to sleep so rapidly. A year later, his lab resolved a 20-year mystery, the mechanism of action of the stimulant modafinil used in the treatment of narcolepsy. Modafinil was found to increase electrical coupling and coherence of cell activity in the same centers found to manifest electrical coupling, increasing arousal . All of these breakthroughs are addressed in review articles from Garcia-Rill lab appearing in this issue of Sleep Science . However, these major contributions are only the tip of the iceberg. About 5 years ago, Garcia-Rill first reported the presence of gamma band activity in these arousal-related centers, suggesting that this system generates its own high frequency activity . They went on to show that this activity was mediated by intrinsic membrane oscillations due to the presence of high threshold voltage-dependent N- and P/Q-type calcium channels . This year, they found that a protein over expressed in schizophrenia and bipolar disorder blocks the manifestation of gamma band activity in the PPT . They also showed that one of the mechanisms by which lithium has a therapeutic effect is because it blocks the over expressing protein to allow the maintenance of gamma band activity, which is reduced in these disorders. So much for the 60-year mystery of the action of lithium. These findings are described in his Sleep Science review on schizophrenia and bipolar disorder, which are characterized by serious sleep-wake disturbances. Also this year, the Garcia-Rill group reported the presence in the PPT of different populations of cells with only N-type, only P/Q-type, or both N- and P/Q-type calcium channels . These populations may correspond to in vivo studies showing “REM-on”, “Wake-on” and “Wake/REM-on” cells, respectively, resolving a 30-year mystery . This segregation suggests that waking and REM sleep are controlled by two separate intracellular pathways, which we investigated for many years . This discovery implies that the gamma band activity observed during waking is different from that seen during REM sleep. In his Sleep Science review on insomnia , Garcia-Rill proposes a novel mechanism for this disorder (excessive waking due to increased expression or activity in the CaMKII-P/Q-type channel system). This imaginative proposal provides excellent new therapeutic targets for this difficult to treat condition.
Introduction A 23 year old man was referred to our sleep clinic with a history of loud snoring, witnessed apnoeas and waking with a dry and sore throat. He experienced daytime somnolence, scoring 18/24 on the Epworth Sleepiness Scale and reported significant impairment in concentration and memory. He was mildly overweight (body mass index 28.2kg/m2, neck circumference 39.5cm) and had a resting oxygen saturation of 100%. In addition he was awaiting adenoidectomy and tonsillectomy due to an enlarged tonsil on the right side and enlarged adenoids, and described “attacks” of sudden-onset bilateral nasal obstruction which varied in duration. A diagnosis to confirm or exclude obstructive sleep apnoea was required in order for surgery to proceed.