Journal of Dementia
Open Access

Our Group organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations
700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)
  • Review Article   
  • J Dement 2017, Vol 1(1): 104

Neurochemicals and Behavioural Alterations in Sleep Deprivation: A Revisit

Parameswari PR1, Chethan N2 and Saravana Babu Chidambaram2*
1SRU Centre for Indian Systems of Medicine Quality Assurance and Standardisation, Sri Ramachandra University, Chennai, India
2JSS College of Pharmacy, Jagadguru Sri Shivarathreeswara University, India
*Corresponding Author: Saravana Babu Chidambaram, Associate Professor, Department of Pharmacology, JSS College of Pharmacy, Jagadguru Sri Shivarathreeswara University, India, Tel: +91-9940434129, Email: csaravanababu@gmail.com

Received: 19-Oct-2017 / Accepted Date: 30-Oct-2017 / Published Date: 10-Nov-2017

Abstract

Sleep is an invigorative biological process which cannot be defined as such, but is organized through intricate interactions between various brain regions and neurochemistry. Sleep endures physical and cognitive performance, health and well-being; even mild sleep restriction degrades behavioural performance over a few days. Sleep deprivation (SD) leads to an array of disorders such as cognitive dysfunctions, attention deficits including coordination and concentration. A decrease in the cortical sensitivity to an incoming stimuli leads to defect in attention. Also sleep deprivation leads to elevated levels of excitatory neurotransmitters and abnormalities in certain other neuromodulators which ultimately has effects on neuronal and executive functions. Inspite of wide-cut literatures availability on the neurochemical deviations following sleep deprivation, this review focuses on the major neurotransmitters effects leading to behavioural alterations and the concomitant brain region activities.

Keywords: Sleep; Sleep deprivation; Neurotransmitters; Cognition; Behaviour; Neurobiology

Introduction

Sleep comprises almost one-third of human life and is common to all animal species, yet its impact on health and medical conditions remains unknown [1]. Sleep should be viewed in the context of other forms of “adaptive inactivity” and is subdivided into rapid eye movement (REM) sleep, characterized by high-frequency electroencephalogram (EEG) recordings and muscle atonia and non-REM (NREM/slow wave) sleep, characterized by low frequency EEG recordings and body rest [2,3]. What is most remarkable about sleep is not the impassiveness or vulnerability it creates, but rather its ability to reduce activity and the body and brain metabolism [4]. The quality of life, performance, and mental well-being are all adversely affected by even a single night’s loss of sleep. Sustained sleep deprivation (SD) impairs central thermostat, metabolism and immune functions, and leads ultimately to death. Accumulated sleep pressure caused by prolonged wakefulness can impair cognitive function [5]. SD is prevalent in various occupations and individuals including shift workers, medical personnel, military, children who do not have regular sleep cycles, and individuals with sleep disorders. SD in human is broadly classified into three categories: total sleep deprivation (TSD), partial sleep deprivation (PSD) and sleep fragmentation. TSD is the complete lack of sleep for at least one night and often longer. PSD involves restricted sleep for multiple nights, that is, individuals obtaining an inadequate amount of sleep for several consecutive nights. Sleep fragmentation is repeated awakenings from sleep throughout the night. This result in a decreased amount of sleep but a normal time spent in bed [6].

Empirical reports on neurophysiological and biochemical methods explain the fundamental mechanisms underlying sleep regulation. Neurophysiological methods helped in identification of circuits involved in NREMS regulation, such as corticothalamic projections and the hypothalamic ventrolateral preoptic and median preoptic circuits, and the REMS regulation, such as laterodorsal tegmental nucleus. Satisfactory explanations of how these circuits impose sleep on the brain and how they keep track of past sleep–wake activity likely will involve the biochemical mechanisms that interact with these circuits [7]. The control mechanism of sleep are established at every level of biological organization, from genes and intracellular mechanisms to networks of cell populations, and to all central neuronal systems at the organismic level, including those that control movement, arousal, autonomic functions, behaviour and cognition [8]. Experimental data have shown that many brain regions possess specific functions in sleep at its each structural level. Strong evidences suggest that sleep is homeostatically regulate, it possess beneficial effects on cognitive functions and it helps in memory consolidation and desaturate the ability to learn [9-13].

This review focuses on the consequences of chronic sleep restriction on brain vulnerability, with characteristic emphasizing on systems that have been associated in psychopathology. Literatures suggest that deprivation in sleep increases the risk to develop psychopathology, although the mechanisms underlying this effect are largely unknown. Loss of sleep could increase the risk for psychopathology acting on various neurobiological systems. The review focuses on the effects of sleep loss on neuromodulatory effects leading to behavioural alterations and the concomitant brain region activities.

Sleep Deprivation And Neurotransmitters

The most conspicuous changes that occur during sleep loss are the neuromodulatory transitions and effective control of these transitions is critical for fitness and survival. In the brain, activity of neuromodulatory neurons, grouped within nuclei of the midbrain and brainstem, co-varies with the psychological and physiological factors, thereby mediating behavioural state in the central nervous system. This is how cognitive processes, including focused attention, learning, memory, and even perception are impacted by the behavioural state [14]. The subcortical neuromodulatory circuits involved in sleepwake control also play important roles in the regulation of arousal and attention, and malfunctioning of these circuits causes a variety of cognitive impairments.

The ascending activating reticular system (ARAS) projecting to the thalamus, hypothalamus, basal forebrain, and neocortex in the brain are the critical regions in sustaining wakefulness and responsible for cortical activation. This ascending system of brain comprises the major brain neuromodulatory systems–acetylcholine (ACh), dopamine (DA), norepinephrine (NE), and serotonin (5-HT) all but DA are under strict regulation across the sleep cycle. In waking, these neuromodulators are released at high levels, activating the inositol triphosphate/diacylglycerol (IP3/DAG) and cyclic AMP secondmessenger systems, thereby reducing neuronal K+, causing neurons to be tonically depolarized [15]. In REM sleep, this same result is achieved by release of acetylcholine alone, as release of serotonin and norepinephrine in REM sleep is minimal [16-18]. In non-REM sleep, these neuromodulators are all released at relatively low levels, and hence neurons are relatively hyperpolarized in this state.

Cholinergic System

Acetylcholine (ACh) is a fast-acting, steeplechase cholinergic neurotransmitter present at the neuromuscular junction and in the autonomic ganglia [19]. Pontomesencephalic tegmentum projection, laterodorsal tegmentum, medial habenula, thalamus, hypothalamus and the basal forebrain (BF) complex including the medial septum contains ACh -containing neurons [20-23]. These cholinergic neurons apart from its role in wakefulness have been included in control of much wake-promoting behaviours such as attention, sensory procession and learning. It was found that behaviourally pertinent signals from the sensory inputs induce a transient increase in the PFC ACh levels and the subsequent activation of cholinergic transmission improves the performance of sustained attention task [24].

ACh changes the neuronal excitability, influences synaptic transmission, induces synaptic plasticity, and coordinates firing of groups of neurons. ACh signals through two classes of receptors: metabotropic muscarinic receptors (mAChRs) and ionotropic nicotinic receptors (nAChRs) [25,26]. Inhibition of cholinergic nuclei resulting in reduced cortical levels of ACh is a major effect caused by SD. SD discharges these Ach-containing neurons which fires at lower rate during slow wave sleep and at higher rates during paradoxical SD [27]. Ninety-six hours of REM sleep deprivation increases acetyl cholinesterase in the pons, thalamus, and medulla oblongata, but not in other brain regions including the hippocampus. It is important to note that the pons contains cholinergic cells involved in the generation of REM, while the thalamus and medulla oblongata receive cholinergic input from the pons. The higher levels of acetyl cholinesterase suggest that there is a higher turnover of acetylcholine in these regions as a consequence of SD [28].

Empirical reports on neurotoxin induced lesions on FB cholinergic neurons further edify the pivotal role of ACh in learning and memory tasks which showed that decrease in ACh leads to certain behavioural deficits. Experimental studies for cognition involving locomotors activation showed correlation between levels of ACh and motor activity. The cholinergic neurons are also highly active during REM sleep [29-31]. The descending projections from cholinergic neurons in the brainstem inhibit motor neurons producing atonia. ACh improves cortical plasticity in adult mammals, and has been suggested that ACh may modulate molecular mechanisms of memory consolidation [32].

The role of ACh in learning and memory has been reviewed by Hasselmo [33]. It was proposed that high ACh biases the system for memory encoding, while low levels bias the system towards recall. ACh levels in the hippocampus are significantly greater during REM than during wake, while neocortical levels are similar in the two states. High levels of ACh release block K+ channels, depolarizing membrane potential and increasing membrane resistance. Impairment of attention which is vital for almost all the cognitive processes occurs due to SD and this neuromodulator is especially linked to vigilance and attention [34]. Sustained attention otherwise termed as vigilance refers to constant allocation of processing resources for detecting an important event. Diminishment in the process of sustained attention performance is widely thought out to be the most sensitive and simple way of measuring behavioural deficit produced by sleep disruption [35]. Hence, sustained attention impairments are widely used as an indirect measure of sleepiness.

ACh has impact on synaptic plasticity and dynamics of local circuits through astrocytic control of synaptic Ca2+ concentration following nAChR stimulation [36]. Astrocytic signalling can lead to LTP as a result of the temporal coincidence of the postsynaptic activity and the astrocyte Ca2+ signal simultaneously evoked by cholinergic stimulation [37]. Receptor expression studies have indicated that REM sleep deprivation reduces muscarinic M2 cholinergic receptors in the pons and hippocampus [38]. The prominent role of cholinergic system in selective attention was well shown by the effects of attention and activation of forebrain. The activation of basal forebrain causes decreased interneuronal correlation and increased sensory–driven response dependability in the visual cortex. This decline in the cortex interneuronal correlation was found to be mediated by mAchRs whereas the improved visual response was found to be mediated by nAChRs-dependent amplification of thalamocortical transmission and/or mAChR-dependent firing rate increase within the cortex [39-41]. Further reports by Parikh et al. suggests that cholinergic transmission can be regulated in a task dependent manner add up the credibility of its involvement in attentional modulation.

Serotonergic System

The Serotonergic system is subtle to sleep loss and serotonin (5-hydroxytryptamine, 5-HT), play a possible role in sleep deprivation. Extracellular 5-HT levels are highest in waking, lower in SWS, and lowest in REM sleep, in all brain regions, including the frontal cortex and the hippocampus [42-44]. Anti-depressant studies showed dysfunction of serotonin and that most antidepressant drug therapies are thought to act by increasing serotonergic neurotransmission [45]. Altered intracellular and extracellular 5-HT concentration during development and adulthood periods lead to increased anxiety and stress-related behaviours [46,47].

5-HT possess a multifaceted system of different receptor subtypes, through which it is involved in the regulation of emotional, neuroendocrine, cognitive and motor functions in the central nervous system (CNS) [48-50]. The localization of serotonin receptors in central motor-related centers also suggest that they are involved in locomotors activity, probably by modulating the release of neurotransmitters such as γ- amino butyric acid (GABA) from striatal neuron terminals [51]. Both depotentiation and habituation to an environment where inhibited by 5-HT agonist application [52]. 5-HT agonist application also improved acquisition but impaired memory consolidation [53].

In a study by Toru et al. it was observed that the tissue concentration of 5-hydroxyindoleacetic acid (5-HIAA), the principal 5-HT metabolite was elevated in the dorsal raphe nucleus and thalamus of rats that were deprived of sleep for 24 h. SD also enhances the serotonin turnover and decreases serotonin transporter binding in some brain areas. Furthermore, total sleep deprivation in cats increases mean firing rates of serotonergic neurons in the dorsal raphe nucleus by 18% [54-57]. The effects of chronic sleep loss on the serotonergic neurons are not well known; however, chronic sleep restriction in animals has been shown to cause a gradually developing desensitization of the Serotonin-1A receptors (5-HT1A) [58,59]. It has been suggested that this effect could be the result of the repeated stimulation of these receptors due to an enhanced serotonin release. The increased serotonin release during SD occurs in a manner independent of stress [60]. The spontaneous activity of serotonergic neurons throughout the brainstem is strongly dependent on the behavioural state. Serotonin also inhibits cholinergic transmission in basal forebrain (BF), thereby creating sleep homeostatic pressure in the BF [61].

Among its different 5-HT receptors, 5-HT1 and 5-HT2 types are the ones studied most in relation to vigilance. Reduced serotonergic transmission and reduced sensitivity of the 5-HT1A receptor system represent a potential pathway through which sleep loss may alter neuronal plasticity and enhance the sensitivity to neurodegeneration. Desensitization of 5-HT1A receptor caused due to chronic sleep deprivation leads to neurodegeneration [62]. Literatures show that both metabotropic and ionotropic 5-HT1A receptors are involved in learning and memory as well as in a wide array of cognitive disorders and emotional dysregulation [63-65]. Mice lacking the 5-HT1A receptor have been shown to have increased anxiety, as shown by decreased time in the open arms of the elevated plus maze test [66]. 5-HT2ARs are found in the cortex and basal ganglia, and mediate certain behavioural syndromes. 5-HT2 receptors (A, B and C subtypes) activate phospholipase C (PLC), and can be considered excitatory. Out of these three subtypes 5-HT2C receptor plays an important role in regulation of synaptic plasticity, as it activates the phosphorinositol signalling pathway thereby leading to L-type Ca2+ channels opening following release of calcium stores. These data suggest a role of serotonin in the effect of sleep deprivation. In addition to this, 5–HT is also implicated in a variety of behaviours including hunger/feeding, aggression, anxiety and mood.

Noradrenergic System

Norepinephrine (NE) is one of the main neurotransmitters involved in arousal. Being an initiator for maintaining sustained periods of alert waking, the noradrenergic system could be a suitable and prospective target in the treatment of sleep-wake disorders. Lateral hypothalamus, basal forebrain and the cerebral cortex comprises noradrenergic neurons. Neurons of the brainstem nucleus locus coeruleus are the sole source of noradrenaline, a neuromodulator that has a key role in all of these forebrain activities such as sleep–wake cycle and other stress responses [67].

NE levels increase early in both total and REM sleep deprivation. NE can enable various forms of activity-dependent synaptic plasticity and can stimulate gene transcription. NE seems to be essential for working memory and focusing of attention [68,69]. Finally, there is a growing body of evidence from rodent, primate, and human studies that the LC-noradrenergic system plays an imperative role in attentional shifting and behavioural flexibility [70-74]. It was shown in a recent study that the LC noradrenergic neurons during NREM sleep possess increased firing rates which in turn enhance synaptic plasticity and facilitate memory consolidation [75,76].

Dopamine β-hydroxylase knockout (Dbh -/-) mice lacking NE showed altered sleep and arousal patterns. They show decreased latency to sleep after stress, require stronger stimuli to wake them after sleep deprivation, and have increased overall sleep, in a 24 h period [77-79]. REM SD exhibited a considerable decline in single–unit activity of noradrenaline in cat and concentration of noradrenaline in rat when measured in locus coeruleus (LC) [80,81]. Noradrenergic neurons are tonically active in all states except REM sleep. They influence synaptic excitability and plasticity and fall uniquely silent during REM sleep.

The decrease or absence of NE due to SD leads to depotentiation, and either stimulation of the noradrenergic cells of the locus coeruleus (LC), or direct intracerebroventricular application of NE enhances and prolongs LTP [82]. A longer REM SD (72 h) led to an elevated noradrenaline concentration and turnover in the rat LC [83,84]. Furthermore, the waking-induced expression of transcription factors and neurotrophins in rat cerebral cortex, which depends on noradrenergic input, is maintained during 3-8 h of total SD [85].

The LC-NE system plays a prominent role in the regulation of immediate early genes (IEGs); genes which is up-regulated selectively during short (3 h) period of wakefulness. Systemic administration of α2-noradrenergic receptor antagonist or direct infusion of NE increases the NE level with subsequent increase in IEGs such c-fos, nur77, tis-7, tis-21 and zif-268. This suggests that the LC-NE system by regulating the IEGs, plays a perceptible role in the regulation of longterm plasticity and behavioural plasticity of forebrain circuits [86,87]. The correlation between sustained attention (vigilance) and forebrain activity patterns is measured in terms of EEG and it might be drawn to a conclusion that the relationship between EEG and forebrain activity pattern would have curtailed from the modulatory actions of LC-NE [88]. An increased level of NE was found in response to stressors such as alarming, threatening or even noxious. Similarly the crucial role of LC-NE system in behavioural and EEG indices of waking are well documented by suppression of LC neuronal discharge activity and NE activity which is caused by systemic administration of α2-agonist [89,90].

Dopaminergic System

Dopamine acts as a key neurotransmitter which plays a pivotal role in regulation of motor and limbic functions. Experimental reports show evidence that dopamine (DA) modulates wakefulness exerting a wake promoting action. An increased level of DA was observed during waking as well as in association with behavioural arousal [91]. Empirical reports also suggest that the mesolimbic dopaminergic (ML-DA) reward system is activated during sleep. Neurophysiological studies in animals have revealed that regions of the ML-DA circuit such as the nucleus accumbens and the ventral tegmental area show increased bursting neural activity during rapid-eye movement (REM) sleep and a role of dopamine in the generation of REM sleep has been suggested [92-94]. Also increased levels of DA in the ML–DA system during sleep have been suggested to play a pivotal role in the generation of dreams [95,96].

Several behavioural alterations induced by sleep deprivation are associated with the dopaminergic system [97-100]. The nigrostriatal dopamine (DA) pathway mediates activation of motor activity, including exploration, which may promote waking and inhibit sleep, although the discharge of nigral neurons is not dependent on vigilance states. DA plays an important role in the control of fine motor actions and higher cognitive functions such as learning, working memory, attention, decision making, and appetitive and consummatory aspects of reward.

Mice lacking dopamine transporter gene and thus having increased synaptic concentrations of dopamine had threefold waking amount [101]. The effect of dopamine on sleep-wakefulness may often be secondary to influences on motor activity and emotions. In 1978, Tufik and colleagues demonstrated an enhancement in DA receptor sensitivity after REM sleep deprivation in rats and also a significant increase in stereotypic behaviours, including biting, rearing and hypothermia in rats. In fact, PSD increased D2 binding in the striatum and nucleus accumbens in rats [102]. Their results were complemented by Dzirasa et al. whose study demonstrated that dopamine play a central role in regulating sleep-wake states and that the action is mediated by the D2 dopamine receptor pathway. Studies using dopamine-receptor deficient mice or animals injected with an antisense vector demonstrate that dopamine D1 and D2 receptors facilitate behavioural arousal, while D3 receptors mediate the opposite effect. D1 and postsynaptic D2 receptor agonists increase behavioural arousal and waking, and decrease sleep [103].

The down regulation of D2/D3R in ventral striatum under SD conditions, in addition to contributing to reduced wakefulness, could also affect other behaviours. Specifically, DA stimulation of D2/D3R in ventral striatum is implicated in attention and thus D2/D3R down regulation could contribute to the inattentiveness observed with SD [104-106]. Acute sleep deprivation in rats increased goal-directed behaviours toward cocaine. In humans, SD increases the risk of substance abuse and appetitive behaviour [107-109]. This increase in impulsivity and reward seeking post-SD may reflect a compensatory mechanism to adjust for the down regulation of D2 and D3 receptors in the ventral striatum immediately after SD. This down regulation of D2 and D3 receptors might lead to impairment in performance, reward learning and decision making after SD. In line with this interpretation, Hanlon et al. demonstrated that REMSD reduces the rate of responding to the acquisition and maintenance of an operant task for food reward in rats, which might be due to a suppression of dopamine activity in the nucleus accumbens during REMSD [110,111]. In addition, total SD can disrupt the reconsolidation of morphine reward memory [112].

GABAergic System

γ-Amino Butyric acid (GABA) is the most prominent inhibitory neurotransmitter in the brain mediating inhibitory post synaptic potentials [113]. SD induced stress has been reported to alter the content of GABA neurotransmitter in the animals suggesting role of GABAergic mechanism in the sleep deprivation-induced changes in behaviour alterations and oxidative damage in the animals [114,115]. SD causes significant alterations in GABA contents as well as an elevation of L-glutamic acid decarboxylase (GAD) activity [116].

Fast synaptic inhibition in the adult brain is primarily mediated by γ-amino butyric acid receptors (GABArs). Regulation of GABAA receptor surface expression at synapses is a process that is critical for maintaining the correct level of synaptic inhibition and is important for memory consolidation [117]. Wang et al. reported higher GABA levels in cortex, hypothalamus, and brain stem after 72 h of sleep deprivation in mice. This suggested that sleep deprivation might increase GABA tone, leading to increased GABAergic signalling and a suppression of activity of excitatory neurons [118]. Modirrousta et al. showed that expression of the GABAr β2–3 subunit is enhanced in cholinergic cells in the basal forebrain after sleep deprivation, suggesting that one way through which prolonged wake reduces cholinergic activity is through higher GABAergic activity [119]. Increases in GABABr receptor protein levels in hippocampal lysates after 12 h of sleep deprivation using the gentle handling method have also been reported by others [120-124].

Conclusion

Among the greatest challenges currently facing neuroscientists throughout the world, is the quest for a better understanding of the neurophysiologic factors in the central regulatory mechanisms of sleep and of the mechanism of the transition between one stage of sleep and another. Several reports show that there are presently a growing numbers of neurotransmitter agents, proposed neurotransmitter systems and suspected neurotransmitter agents, in the subject of sleep regulatory mechanism. Meanwhile, this review has helped to highlight a number of the neurotransmitter systems that have featured more prominently and frequently and can be said to be currently the more under study by researchers, as well as highlighted the brain areas in which each neurotransmitter systems appears to have featured more significantly in the subject of the central regulator mechanism of sleep.

References

  1. Remy P, Doder M, Lees A, Turjanski N, Brooks D (2005) Depression in Parkinson’s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 128: 1314-1322.
  2. Stenberg D (2007) Neuroanatomy and neurochemistry of sleep. Cell Mol Life Sci 64: 1187-204.
  3. Siegel MJ (2009) Sleep in Animals: A State of Adaptive Inactivity 10: 747-753.
  4. Yoo SS, Hu PT, Gujar N, Jolesz FA, Walker MP (2007) A deficit in the ability to form new human memories without sleep. Nat Neurosci 10: 385-392.
  5. Drummond SPA, McKenna BS (2009) Sleep deprivation and brain function. In: Stickgold R, Walker M editors. The Neuroscience of sleep USA: Elsevier, p: 249.
  6. Krueger JM, Churchill L, Rector DM (2009) Sleep and Sleep States: Cytokines and Neuromodulation. In: Squire LR editor. Encyclopedia of Neuroscience 8: 905-911.
  7. Pace-Schott EF, Hobso JA (2002) in American College of Neuropsychopharmacology, Fifth Generation of Progress. Charney D, Coyle J, Davis K, Nemeroff C editors. pp: 1859-1877.
  8. Dinges DF, Pack F, Williams K, Gillen KA, Powell JW, et al. (1997) Cumulative sleepiness, mood disturbance and psychomotor vigilance performance decrements during a week of sleep restricted to 4-5 hours per night. Sleep 20: 267-277.
  9. Van Dongen HPA, Maislin G, Mullington JM, Dinges DF (2003) The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep 26: 117-126.
  10. Maquet P (2001) The role of sleep in learning and Memory. Science 294: 1048-1052.
  11. Steriade M, McCarley RW, Plenum Stickgold R (2005) Brain Control of Wakefulness and Sleep. New York: Sleep-dependent memory consolidation. Nature 437: 1272-1278.
  12. Walker MP, Stickgold R(2004) Sleep-dependent learning and memory consolidation. Neuron 44: 121-133.
  13. Sara JS, Bouret S (2012) Orienting and Reorienting: The Locus Coeruleus mediates cognition through arousal. Neuron 76: 130-141.
  14. Hirsch JC, Fourment A, Marc ME (1983) Sleep-related variations of membrane potential in the lateral geniculate body relay neurons of the cat. Brain Res 259: 308-312.
  15. Aston-Jones G, Bloom FE (1981) Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep–waking cycle. J Neurosci 1: 876-886.
  16. Jacobs BL (1986) Single unit activity of locus coeruleus neurons in behaving animals. Prog Neurobiol 27: 183-194.
  17. McGinty DJ, Harper RM (1976) Dorsal raphe neurons: depression of firing during sleep in cats. Brain Res 101: 569-575.
  18. Changeux JP (2010) Allosteric receptors: from electric organ to cognition. Ann Rev Pharmacol Toxicol 50: 1-38.
  19. Ren J, Qin C, Hu F, Tan J, Qiu L (2011) Habenula “cholinergic” neurons co-release glutamate and acetylcholine and activate postsynaptic neurons via distinct transmission modes. Neuron 69: 445-452.
  20. Zaborszky L (2002) The modular organization of brain systems. Basal forebrain: the last frontier. Progr Brain Res 136: 359-372.
  21. Zaborszky L, Hoemke L, Mohlberg H, Schleicher A, Amunts K, et al. (2008) Stereotaxic probabilistic maps of the magnocellular cell groups in human basal forebrain. Neuroimage 42: 1127-1141.
  22. Parikh V, Kozak R, Martinez V, Sarter M (2007) Prefrontal acetylcholine release controls cue detection on multiple timescales. Neuron 56: 141-154.
  23. Picciotto MR, Caldarone BJ, King SL, Zachariou V (2000) Nicotinic receptors in the brain. Links between molecular biology and behavior. Neuropsychopharmacology 22: 451-465.
  24. Wess J (2003) Novel insights into muscarinic acetylcholine receptor function using gene targeting technology. Trends in Pharmacological Sciences 24: 414-420.
  25. Woolf NJ (1997) A possible role for cholinergic neurons of the basal forebrain and pontomesencephalon in consciousness. Conscious Cogn 6: 574-596.
  26. Benedito MA, Camarini R (2001) Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions. Brazilian Journal of Medical and Biological Research 34: 103-109.
  27. Maloney KJ, Mainville L, Jones BE (1999) Differential c-Fos expression in cholinergic, monoaminergic, and GABAergic cell groups of the pontomesencephalic tegmentum after paradoxical sleep deprivation and recovery. J Neurosci 19: 3057-3072.
  28. McCarley RW, Hobson JA (1975) Neuronal excitability modulation over the sleep cycle: a structural and mathematical model. Science 189: 58-60.
  29. Steriade M, Datta S, Pare D, Oakson G, Curro Dossi RC (1990) Neuronal activities in brain- stem cholinergic nuclei related to tonic activation processes in thalamocortical systems. J Neurosci 10: 2541-2559.
  30. Graves L, Pack A, Abel T (2001) Sleep and memory: A molecular perspective. Trends in Neuroscience 24: 237-243.
  31. Hasselmo ME (1999) Neuromodulation: Acetylcholine and memory consolidation. Trends in Cognitive Science 3: 351-359.
  32. Balkin TJ, Rupp T, Picchioni D, Wesensten NJ (2008) Sleep loss and sleepiness. Current issue 134: 653-660.
  33. Balkin TJ, Bliese PD, Belenky G, Sing H, Thorne DR, et al. (2004) Comparative utility of instruments for monitoring sleepiness-related performance decrements in the operational environment. Journal of Sleep Resea 13: 219-227.
  34. Takata N, Mishima T, Hisatsune C, Nagai T, Ebisui E, et al. (2011) Astrocyte calcium signaling transforms cholinergic modulation to cortical plasticity in vivo. J Neurosci 31: 18155-18165.
  35. Navarrete M, Perea G, Fernandez de Sevilla D, Gómez-Gonzalo M, Nunez A, et al. (2012) Astrocytes mediate in vivo cholinergic-induced synaptic plasticity. PLoS Biol 10: e1001259.
  36. Salin-Pascual RJ, Diaz-Munoz M, Rivera-Valerdi L, Ortiz-Lopez L, Blanco-Centurion C (1998) Decrease in muscarinic M2 receptors from synaptosomes in the pons and hippocampus after REM sleep deprivation in rats. Sleep Research Online 1: 19-23.
  37. Disney AA, Aoki C, Hawken MJ (2007) Gain modulation by nicotine in macaque v1. Neuron 56: 701-713.
  38. Herrero JL, Roberts MJ, Delicato LS, Gieselmann MA, Dayan P, et al. (2008) Acetylcholine contributes through muscarinic receptors to attentional modulation in V1. Nature 454: 1110-1114.
  39. Soma S, Shimegi S, Osaki H, Sato H (2012) Cholinergic modulation of response gain in the primary visual cortex of the macaque. Journal of Neurophysiology 107: 283-291.
  40. Portas CM, Bjorvatn B, Ursin R (2000) Serotonin and the sleep/wake cycle: special emphasis on microdialysis studies. Prog Neurobiol 60: 13-35.
  41. Portas CM, Rees G, Howseman AM, Josephs O, Turner R (1998) A specific role for the thalamus in mediating the interaction of attention and arousal in humans. J Neurosci 18: 8979-8989
  42. Park SP, Lopez-Rodriguez F, Wilson CL, Maidment N, Matsumoto Y, et al. (1999) In vivo microdialysis measures of extracellular serotonin in the rat hippocampus during sleep-wakefulness. Brain Res 833: 291-296
  43. Blier P, De Montigny C (1994) Current advances and trends in the treatment of depression. Trends Pharmacol Sci 15: 220-226.
  44. Murphy DL, Lesch KP (2008) Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci 9: 85-96.
  45. Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA (2004) Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 306: 879-881.
  46. Martin GR, Humphrey PP (1994) Receptors for 5-hydroxytryptamine: current perspectives on classification and nomenclature. Neuropharmacology 33: 261-73.
  47. Dinan TG (1996) Serotonin: Current understanding and the way forward. Int Clin Psychopharmacol 11: 19-21.
  48. Monti JM, Jantos H (2008) The roles of dopamine and serotonin, and of their receptors, in regulating sleep and waking. Prog Brain Res 172: 625-646.
  49. Maroteaux L, Saudou F, Amlaiky N, Boschert U, Plassat JL, et al. (1992) Mouse 5HT1B serotonin receptor: cloning, functional expression, and localization in motor control centres. Proc Natl Acad Sci USA 89: 3020-3024.
  50. Kemp A, Manahan-Vaughan D (2004) Hippocampal long-term depression and long-term potentiation encode different aspects of novelty acquisition. Proc Natl Acad Sci USA 25: 8192-8197.
  51. Meneses A, Hong E (1997) Effects of 5-HT4 receptor agonists and antagonists in learning. Pharmacol Biochem Behav 56: 347-351.
  52. Asikainen M, Toppila J, Alanko L, Ward DJ, Stenberg D, et al. (1997) Sleep deprivation increases brain serotonin turnover in the rat. Neuroreport 8: 1577-1582.
  53. Senthilvelan M, Ravindran R, Samson J, Devi RS (2006) Serotonin turnover in different duration of sleep recovery in discrete regions of young rat brain after 24 h REM sleep deprivation. Brain Dev 28: 526-528.
  54. Andersen ML, Papale LA, Hipolide DC, Nobrega JN, Tufik S (2005) Involvement of dopamine receptors in cocaine-induced genital reflexes after paradoxical sleep deprivation. Behav Brain Res 160: 44-50.
  55. Gardner JP, Fornal CA, Jacob BL (1997) Effects of sleep deprivation on serotonergic neuronal activity in the dorsal raphe nucleus of the freely moving cat. Neuropsychopharmacology 17: 72-81.
  56. Roman V, Walstra I, Luiten PGM, Meerlo P (2005b) Too little sleep gradually desensitizes the 5-HT1A receptor system in rats. Sleep 28: 1505-1510.
  57. Roman V, Van der Borght K, Leemburg S, Van der Zee EA, Meerlo P (2005a) Sleep restriction by forced activity reduces hippocampal cell proliferation. Brain 1065: 53-59.
  58. Zant JC, Leenaars CHC, Kostin A, Van Someren EJW, Porkka-Heiskanen T (2011) Increases in extracellular serotonin and dopamine metabolite levels in the basal forebrain during sleep deprivation. Brain Res 1399: 40-48.
  59. Hoyer D, Hannon JP, Martin GR (2002) Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 71: 533-554.
  60. Ogren SO, Eriksson TM, Elvander-Tottie E, D’Addario C, Ekström JC, et al. (2008) The role of 5-HT1A receptors in learning and memory. Behav Brain Res 195: 54-77.
  61. Gross C, Hen R (2004) The developmental origins of anxiety. Nat Rev Neurosci 5: 545-552.
  62. Gross C, Zhuang X, Stark K, Ramboz S, Oosting R, et al. (2002) Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature 416: 396-400.
  63. Zhuang X, Gross C, Santarelli L, Compan V, Trillat AC, et al. (1999) Altered emotional states in knockout mice lacking 5-HT1A or 5-HT1B receptors. Neuropsychopharmcology 21: 52-60.
  64. Gonzalez MM, Debilly G, Valatx JL (1998) Noradrenaline neurotoxin DSP-4 effects on sleeps and brain temperature in the rat. Neurosci Lett 248: 93-96.
  65. Ramos BP, Arnsten AF (2007) Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther 113: 523-536.
  66. Arnsten AFT, Wang MJ, Paspalas CD (2012) Neuromodulation of thought: flexibilities and vulnerabilities in prefrontal cortical network synapses. Neuron 76: 223-239.
  67. Devauges V, Sara SJ (1990) Activation of the noradrenergic system facilitates an attentional shift in the rat. Behav Brain Res 39: 19-28.
  68. Aston-Jones G, Cohen JD (2005) An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 28: 403-450.
  69. Bouret S, Sara SJ (2005) Network reset: a simplified overarching theory of locus coeruleus noradrenaline function. Trends in Neurosciences 28: 574-582.
  70. Yu AJ, Dayan P (2005) Uncertainty, neuromodulation, and attention. Neuron 46: 681-692.
  71. McGaughy J, Ross RS, Eichenbaum H (2008) Noradrenergic but not cholinergic differentiation of prefrontal cortex impairs attentional set-shifting. Neuroscience 153: 63-71.
  72. Sara SJ (2009) The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci 10: 211-223.
  73. Eschenko O, Sara SJ (2008) Learning-dependent, transient increase of activity in noradrenergic neurons of locus coeruleus during slow wave sleep in the rat: brain stem-cortex interplay for memory consolidation? Cereb Cortex 18: 2596-2603.
  74. Hunsley MS, Palmiter RD (2004) Altered sleep latency and arousal regulation in mice lacking norepinephrine. Pharmacol Biochem Behav 78: 765-773.
  75. Hunsley MS, Palmiter RD (2003) Norepinephrine-deficient mice exhibit normal sleep-wake states but have shorter sleep latency after mild stress and low doses of amphetamine. Sleep 26: 521-526.
  76. Ouyang M, Hellman K, Abel T, Thomas SA (2004) Adrenergic signalling plays a critical role in the maintenance of waking and in the regulation of REM sleep. J Neurophysiol 92: 2071-2082.
  77. Mallick BN, Siegel JM, Fahringer H (1990) Changes in pontine unit activity with REM sleep deprivation. Brain Res 515: 94-98.
  78. Porkka-Heiskanen T, Smith SE, Taira T, Urban JH, Levine JE (1995) Noradrenergic activity in rat brain during rapid eye movement sleep deprivation and rebound sleep. Am J Physiol 268: R1456-R1463.
  79. Almaguer-Melian W, Rojas-Reyes Y, Alvare A, Rosillo JC, Frey JU, et al. (2005) Long-term potentiation in the dentate gyrus in freely moving rats is reinforced by intraventricular application of norepinephrine, but not oxotremorine. Neurobiol Learn Mem 83: 72-78.
  80. Perez NM, Benedito MA (1997) Activities of monoamine oxidase (MAO) A and B in discrete regions of rat brain after rapid eye movement (REM) sleep deprivation. Pharmacol Biochem Behav 58: 605-608.
  81. Basheer R, Magner M, McCarley RW, Shiromani PJ (1998) REM sleep deprivation increases the levels of tyrosine hydroxylase and norepinephrine transporter mRNA in the locus coeruleus. Brain Res. Mol Brain Res 57: 235-240.
  82. Cirelli C, Tononi G (2000) Gene expression in the brain across the sleep-waking cycle. Brain Res 885: 303-321.
  83. Dragunow M, Goulding M, Faull RLM (1989) Long-term potentiation and the induction oft-fos mRNA and proteins in the dentate gyrus of unanesthetized rats. Neurosci Lett 101: 274-280.
  84. Hagan JJ, Leslie RA, Patel S, Evans ML, Wattam TA, et al. (1999) Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc Natl Acad Sci U S A 96: 10911-10916.
  85. Makeig S, Inlow M (1993) Lapses in alertness: coherence of fluctuations in performance and EEG spectrum. Electroencephalogr Clin Neurophysiol 86: 23-35.
  86. De Sarro GB, Ascioti C, Froio F, Libri V, Nistico G (1987) Evidence that locus coeruleus is the site where clonidine and drugs acting at alpha 1- and alpha 2-adrenoceptors affect sleep and arousal mechanisms. Br J Pharmacol 90: 675-685.
  87. De Sarro GB, Bagetta G, Ascioti C, Libri V, Nistico G (1989) Effects of pertussis toxin on the behavioural and ECoG spectrum changes induced by clonidine and yohimbine after their microinfusion into the locus coeruleus. Br J Pharmacol 96: 59-64.
  88. Trulson ME (1985) Simultaneous recording of substantia nigra neurons and voltammetric release of dopamine in the caudate of behaving cats. Brain Res Bull 15: 221-223.
  89. Dahan L, Astier B, Vautrelle N, Urbain N, Kocsis B, et al. (2007) Prominent burst firing of dopaminergic neurons in the ventral tegmental area during paradoxical sleep. Neuropsychopharmacology 32: 1232-1234.
  90. Lena I, Parrot S, Deschaux O, Muffat-Joly S, Sauvinet V, et al. (2005) Variations in extracellular levels of dopamine, noradrenaline, glutamate, and aspartate across the sleep–wake cycle in the medial prefrontal cortex and nucleus accumbens of freely moving rats. Journal of Neuroscience Research 81: 891-899.
  91. Dzirasa K, Ribeiro S, Costa R, Santos LM, Lin SC, et al. (2006) Dopaminergic control of sleep-wake states. J Neurosci 26: 10577-10589.
  92. Solms M (2000) Dreaming and REM sleep are controlled by different brain mechanisms. Behavioral Brain Sciences 23: 843-850.
  93. Solms M (2002) Dreaming: cholinergic and dopaminergic hypotheses. John Benjamins Publishing Company, Amsterdam.
  94. Andersen ML, Martins PJF, D’Almeida V, Bignotto M, Tufik S (2005) Endocrinological and catecholaminergic alterations during sleep deprivation and recovery in male rats. J Sleep Res 14: 83-90.
  95. Andersen ML, Perry JC, Tufik S (2005) Acute cocaine effects in paradoxical sleep deprived male rats. Prog Neuropsychopharmacol Biol Psychiatry 29: 245-251.
  96. Andersen ML, Papale LA, Hipolide DC, Nobrega JN, Tufik S (2005) Involvement of dopamine receptors in cocaine-induced genital reflexes after paradoxical sleep deprivation. Behav Brain Res 160: 44–50.
  97. Tufik S, Lindsey CJ, Carlini EA (1978) Does REM sleep deprivation induces a super sensitivity of dopaminergic receptors in the rat brain? Pharmacology 16: 98-105.
  98. Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E (2001) Dopaminergic role in stimulant induced wakefulness. J Neurosci 21: 1787-1794.
  99. Nunes Junior GP, Tufik S, Nobrega JN (1994) Autoradiographic analysis of D1 and D2 dopaminergic receptors in rat brain after paradoxical sleep deprivation. Brain Res Bull 34: 453-456.
  100. Monti JM, Monti D (2007) The involvement of dopamine in the modulation of sleep and waking. Sleep Med Rev 11: 113-133.
  101. Volkow ND, Tomasi D, Wang JG, Telang F, Fowler SJ, et al. (2012) Evidence that Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain. J Neurosci 32: 6711-6717.
  102. Durmer JS, Dinges DF (2005) Neurocognitive consequences of sleep deprivation. Semin Neurol 25: 117-129.
  103. Tomasi D, Wang RL, Telang F, Boronikolas V, Jayne MC, et al. (2009) Impairment of attentional networksafter 1 night of sleep deprivation. Cereb Cortex 19: 233-240.
  104. Shibley HL, Malcolm RJ, Veatch LM (2008) Adolescents with insomnia and substance abuse: consequences and comorbidities. J Psychiatr Pract 14: 146-153.
  105. Wong MM, Brower KJ, Zucker RA (2009) Childhood sleep problems, early onset of substance use and behavioral problems in adolescence. Sleep Med 10: 787-796.
  106. Benedict C, Brooks SJ, O'Daly OG, Almen MS, Morell A (2012) Acute sleep deprivation enhances the brain's response to hedonic food stimuli: an fMRI study. J Clin Endocrinol Metab 97: E443-447.
  107. Hanlon EC, Andrzejewski ME, Harder BK, Kelley AE, Benca RM (2005) The effect of REM sleep deprivation on motivation for food reward. Behavioural Brain Research 163: 58-69.
  108. Hanlon EC, Benca RM, Baldo BA, Kelley AE (2010) REM sleep deprivation produces a motivational deficit for food reward that is reversed by intra-accumbens amphetamine in rats. Brain Research Bulletin 83: 245-254.
  109. Shi HS, Luo YX, Xue YX, Wu P, Zhu WL, et al. (2011) Effects of sleep deprivation on retrieval and reconsolidation of morphine reward memory in rats. Pharmacology Biochemistry and Behavior 98: 299-303
  110. Yourn AB, Chu D (1990) Distribution of GABA-A and GABA-B receptors in the mammalian brain. Drug Dev Res 21: 161.
  111. Kalonia H, Kumar A (2007) Protective effect of melatonin on certain behavioral and biochemical alterations induced by sleep-deprivation in mice. Indian J Pharmacol 39: 48-51.
  112. Kumar A, Kalonia H (2007) Protective effect of Withania Somnifera Dunal on the Behavioral and biochemical alterations in sleep-disturbed mice (Grid over water suspended method). Indian J Exp Biol 45: 524-528.
  113. Mombereau C, Kaupmann K, Froestl W, Sansig G, Putten VH, et al. (2004) Genetic and Pharmacological evidence of a role for GABAB receptors in the modulation of anxiety and antidepressant like behavior. Neuropsychopharmacology 29: 1050-1062.
  114. Tretter V, Revilla-Sanchez R, Houston C, Terunuma M, Havekes R, et al. (2009) Deficits in spatial memory correlate with modified {gamma}-aminobutyric acid type A receptor tyrosine phosphorylation in the hippocampus. 106: 20039-20044.
  115. Modirrousta M, Mainville L, Jones BE (2007) Dynamic changes in GABA receptors on basal forebrain cholinergic neurons following sleep deprivation and recovery. BMC Neuroscience 8: 15.
  116. Wang SX, Li QS, Jun YD, Da Y, Bao XX (2002) Effects of sleep deprivation on gamma-amino-butyric acid and glutamate contents in rat brain. 22: 888-890.
  117. Tadavarty R, Rajput PS , Wong JM, Kumar U, Sastry BR (2011) Sleep-Deprivation Induces Changes in GABAB and mGlu Receptor Expression and Has Consequences for Synaptic Long-Term Depression. PLOS One 6: e24933.
  118. Asikainen M, Deboer T, Porkka-Heiskanen T, Stenberg D, Tobler I (1995) Sleep deprivation increases brain serotonin turnover in the Djungarian hamster. Neurosci Lett 198: 21-24.
  119. Hipolide DC, Moreira KM, Barlow KBL, Wilson AA, Nobrega JN, et al. (2005) Distinct effects of sleep deprivation on binding to norepinephrine and serotonin transporters in rat brain. Prog Neuropsychopharmacol Biol Psychiatry 29: 297-303.
  120. Picciotto M, Higley JM, Mineur SY (2012) Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behaviour. Neuron 76: 116-129.
  121. Tritsch XN, Ding BJ, Sabatini LB (2012) Dopaminergic neurons inhibit striatal output through non-canonical release of GABA. Nature 490: 262-266.
  122. Toru M, Mitsushio H, Mataga N, Takashima M, Arito H (1984) Increased brain serotonin metabolism during rebound sleep in sleep deprived rats. Pharmacol Biochem Behav 20: 757-761.

Citation: Parameswari PR, Nagabushan C, Chidambaram BS (2017) Neurochemicals and Behavioural Alterations in Sleep Deprivation: A Revisit. J Dement 1: 104.

Copyright: ©2017 Parameswari PR, et al.. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Post Your Comment Citation
Share This Article
Recommended Conferences
Article Usage
  • Total views: 8214
  • [From(publication date): 0-2017 - Sep 19, 2024]
  • Breakdown by view type
  • HTML page views: 7406
  • PDF downloads: 808
Top