Priyattam Shiromani

..The findings also indicate that although old rats have a decline in sleep, this cannot be attributed to loss of VLPO neurons implicated in sleep...

..By demonstrating that these IEGs are involved in sleep, we suggest that the deletion of specific genes, even within a family of genes, can have a specific effect on sleep...

..Although mPer1 and mPer2 represent key elements of the molecular clock in the SCN, they are not required for homeostatic regulation of the daily amounts of waking, SWS, or REM sleep...

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..In young rats and monkeys, levels of HCRT-1 are highest at the end of the wake-active period and lowest toward the end of the sleep period. However, the effects of age on the diurnal rhythm of HCRT-1 are not known...

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..All of these neurons were less active during cataplexy compared with REM sleep. Thus, although cataplexy and REM sleep share many common features, including the muscle atonia, cataplexy is a distinct state in mice...

..These findings indicate that adenosine levels do not increase with wakefulness in rats with a HCRT lesion, and that the increased sleep in these rats occurs independently of adenosine levels in the basal forebrain...

..We conclude that orexin is not required for entrainment of activity and temperature to a restricted feeding schedule, but is required for the robust expression of gross locomotor activity in anticipation of the scheduled feeding...

..The loss of hypocretin neurons produced by chronic LPS administration suggests that inflammation may play a role in the loss of hypocretin neurons in narcolepsy...

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..In those narcoleptics where CSF levels are within the normal range, it is possible that not all of the HCRT neurons are lost and that the surviving HCRT neurons might be increasing output of CSF HCRT...

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..These results suggest that, in the absence of the basal forebrain cholinergic neurons, the basal forebrain noncholinergic neurons are able to convey hypocretin's arousal signal unabated...

..Thus, neither the activity of the BF cholinergic neurons nor the accumulation of AD in the BF during wake is necessary for sleep drive...

..CONCLUSION: The absence of gross changes in sleep after extensive loss of histaminergic neurons suggests that this system is not critical for spontaneous wakefulness...

..These findings identify a potential therapeutic use of endocannabinoids to induce sleep in conditions where sleep may be severely attenuated...

..These results indicate that caloric restriction is unable to prevent the decline in sleep that occurs with aging...

..89) with loss of eGFP neurons. These results identify the vlPAG as one site that loses its inhibitory control over REM sleep, but does not cause cataplexy, as a result of hypocretin deficiency...

..We hypothesized that insomniacs would be more affected by caffeine, which would suggest a change in adenosine receptor (number or sensitivity) in primary insomniacs...

..Here we examined the survival of hypocretin-containing neurons grafted into the pontine reticular formation, a region traditionally regarded to be key for rapid eye movement sleep generation...

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..The connections and physiological activity of the extended VLPO suggest a specialized role in the regulation of REM sleep...

..This will determine which receptor subtype containing neurons are affected by the saporin conjugate. Our findings will provide a framework for integrating the hypocretin/orexin cells within an overall model of sleep regulation. ..

..Then 192-lgG saporin will be used in the transgenic rats to lesion the BF cholinergic neurons and we hypothesize that with both the BF cholinergic and HCRT neurons lost, the rats should have more sleep compared to single lesions. ..

..Specific aim 3 will test the hypothesis that loss of a specific population of HCRT neurons is responsible for the symptoms of narcolepsy. Specific aim 4 will determine the afferents and efferents of this population of HCRT neurons. ..

..abstract_text> ..

..Their preliminary results indicate that somnogens such as adenosine induce c-Fos (measured using immunohistochemistry and on tissue slices, and via western blot analysis of basal forebrain tissue homogenate) and AP-1. ..

..The protein might act as a third messenger serving to regulate the functional response of the cell. These studies will establish a groundwork for future work related to the transcriptional processes occuring during REM sleep...

..The PI's studies to date have used c-Fos to identify the neuronal mechanisms generating sleep. To the best of our knowledge no current program is examining transcription factors as playing a role in the disease. ..

..The significance of this project is that it will develop a gene transfer approach that will serve as a neurobiological tool to understand the networking underlying narcolepsy and also to ultimately restore some function. ..