Wakefulness activity

Figure 1.7 Effects of local POA warming on discharges of a DRN, wake-active, REM-off, putative serotonin-containing neuron. POA warming suppressed DRN neuronal discharge, without any change in behavioral state, as shown by EEG spectral analysis. Thus activation of POA WSNs can suppress DRN discharge. The DRN receives direct projections from the POA. From Guzman-Marin el al (2000).

The POA also contains cold-sensitive neurons (CSNs), cells activated by local cooling and inhibited by local warming. Most CSNs are wake-active thus, like arousal-related neurons in PLH, PH, DRN and basal forebrain, they exhibit... 

Figure 1.8 Effects of local POA warming on a PLH wake-active, REM-off, putative hypocretin/orexin-containing neuron. POA warming suppressed the waking-related discharge of PLH neurons, in the absence of any state change. The PLH receives strong projections from all subregions of the POA, including GABAergic projections. From Methippara et al. (2003).

IL-ip is a well documented sleep factor (reviewed by Obal Krueger, 2003). Its administration increases sleep, its blockade decreases sleep and sleep rebound, and its transcription increases during waking. IL-1 receptor knock-out mice sleep less. Local application of IL-1 p in POA also stimulates NREM sleep. We examined the effects of local administration of IL-1 p and an antagonist through microdialytic application adjacent to lateral POA neurons (Alam et at, 2004). Neuronal activity is recorded within 0.5-1.0 mm of a microdialysis membrane in unrestrained rats. IL-ip potently inhibited the activity of 79% of wake-active neurons. The inhibitory response to IL-ip of wake-active neurons could be blocked by pre-treatment with IL-lra, an IL-ip antagonist. IL-ip application also excited some sleep-active neurons, but this response was inconsistent. 

Methippara, M., Alam, Md. N., Szymusiak, R McGinty, D. (2003). Preoptic area warming inhibits wake-active neurons in the perifornical lateral hypothalamus. 

Noradrenaline acts on three types of receptor. The ai receptors mediate the main excitatory effects of noradrenaline upon wake-active neurons in the dorsal raphe, basal forebrain, and elsewhere (Vandermaelen Aghajanian, 1983 Nicoll, 1988 Fort et al., 1995 Brown et al., 2002). The a2 receptors mediate inhibitory effects of noradrenaline, e.g. on noradrenaline neurons themselves and on cholinergic brainstem neurons (Williams et al., 1985 Williams Reiner, 1993). The (3-receptors modulate neurons in a more subtle fashion, increasing excitability via blockade of afterhyperpolarizations in hippocampal and cortical neurons (Haas Konnerth, 1983). Activation of (3-receptors also promotes synaptic plasticity via activation of the cyclic-AMP-dependent kinase (PKA) and cyclic AMP response element binding protein (CREB) signal transduction pathway (Stanton Sarvey, 1987 Cirelli et al., 1996). 

Adenosinergic inhibition of basal forebrain wakefulness-active neurons a simultaneous unit recording and microdialysis study in freely behaving cats. Neuroscience 122, 1107 13. 

In rats, lesions targeting presumptively wake-active dopaminergic neurons that extend dorsally from the VTA into the ventral periaqueductal gray have recently been shown to result in c. 20% reductions in wakefulness (Lu et al. 2006). Daytime sleepiness and SOREMs were reported in a non-human primate following systemic delivery of the dopamine neurotoxin MPTP (Daley et al. 1999), and this was subsequently confirmed in two additional animals (Daley... 

Lu J., Jhou T. C., Saper C. B. (2006). Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray matter. J. Neurosci. 26(1), 193-202. 

Thakkar, M. M., Delgiacco, R. A., Strecker, R. E. McCarley, R. W. (2003a). Adenosinergic inhibition of basal forebrain wakefulness-active neurons a simultaneous unit recording and microdialysis study in freely behaving cats. 

Lee, B., el al. (2002). Prostaglandin D synthase in the prenatal ovine brain and effects of its inhibition with selenium chloride on fetal sleep/wake activity in utero. 

Moreton, J. Edward, Timothy Roehrs, and Naim Khazan. 1976. "Drug Self-Administration and Sleep-Wake Activity in Rats Dependent on Morphine, Methadone, or L-Alpha-Acetylmethadol." Psychopharmacologia 47 237-41. 

Rosenthal L, Roehr TA, Roth T. The sleep-wake activity inventory a self-report measure of daytime sleepiness. Biol Psychiatry 1993 34 810-820. 

In patients with DSPS, a delay in the timing of physiological and behavioral systems that demonstrate circadian rhythmicity is reported, compared to normally entrained individuals. This delay is evident in a variety of functions, including secretion of the pineal hormone melatonin (e.g., Ref. 162), thermoregulation, and sleep-wake activity. Individuals with DSPS typically experience difficulty initiat-... 

Phase advances of the circadian system and sleep-wake activity have been reported in a number of studies, with daily administration of melatonin (180-183). Termination of melatonin administration resulted in a reversal of the phase advances, with subjects reverting to their preadministration phase. Therefore, continued administration of melatonin may provide a means for those with DSPS to maintain a normal phase, and avoid the associated sleep deprivation due to having to live on a normal schedule. It is important to note, however, that at present the effective dose of melatonin to be administered and the safety of long-term melatonin administration have yet to be established (184). Therefore, melatonin should be thought of as a research compound and not a clinical solution to DSPS. 

Gary KA, Winokur A, Douglas SD, Kapoor S, Zaugg L, Dinges DF. Total sleep deprivation and the thyroid axis effects of sleep and waking activity. Aviat Space Environ Med 1996 67 513-519. 

IL-ip and TNF-a promote NREM sleep through multiple brain sites. IL-1 excites sleep-active neurons and inhibits wake-active neurons in the AH/MPO (50). Some hypothalamic neurons are receptive for both IL-ip and GHRH and these neurons are GABAergic (27). IL-ip upregulates hypothalamic GHRH receptors and may also stimulate GHRH synthesis (51). IL-ip injected into the locus ceruleus (52) and dorsal raphe (53) also enhances sleep. Promotion of NREM sleep occurs after microinjection of TNF-a into the AH/MPO (54) or the locus ceruleus (52). 

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