Article

The origin of REM sleep: A hypothesis

Authors:
To read the full-text of this research, you can request a copy directly from the author.

Abstract

This article presents a new theory about the origin of REM sleep. REM is an integral part of the human sleep cycle and the neurological substrate most consistently associated with dreams and dream recall. According to this thesis, REM sleep evolved out of a primordial defensive reflex: tonic immobility. This reflex, sometimes also called death-feigning or animal hypnosis, is usually the last line of defense against an attacking predator. Tonic immobility, common in both vertebrates and invertebrates, has a number of neuroanatomical and behavioral attributes that overlap with those of REM sleep. This overlap is suggestive of an evolutionary kinship. The article presents conceptual arguments and empirical facts in support of this relationship. (PsycINFO Database Record (c) 2013 APA, all rights reserved)

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the author.

... "We are such stuff as dreams are made on, and our little life is rounded with a sleep." William Shakespeare 1.3 REM sleep is a sleep phase common to mammals and birds (i.e., homeothermic animals) characterized by random eye movements, generalized muscle atonia and, in the case of humans, frequent report of vivid dreams upon awakening (around 80% of times, although dreaming activity also occurs during NREM sleep), although it is generally thought that animals exhibiting REM sleep may also dream, albeit in a very different way than humans (Siegel, 2005, Tsoukalas, 2012, Siclari et al., 2014. REM sleep is sometimes also referred as paradoxical sleep due to some shared biological aspects with wakefulness, most notably, low amplitude and fast frequency brain waves in the electroencephalogram, high level of brain activity (particularly in the visual cortex, motor cortex and limbic system) and other hormonal similarities (e.g., in the cortisol levels) (Jones, 2016). ...
... Several studies indicate that the pons (located in the brainstem) is both necessary and sufficient for the generation of REM sleep (Tsoukalas, 2012). Impairment or damage in the frontal lobe might suppress dreaming, but does not interfere with REM activity itself (Siegel, 2011). ...
... Increased REM sleep also occurs when animals are immersed in an enriched environment, although the same holds for SWS (Rasch and Born, 2013). A second theory states that REM sleep evolved out of the tonic immobility reflex (a defense mechanism against predators based on death feigning, also known as animal hypnosis), as it is suggested by numerous biological similarities: low muscle tone, thermoregulatory cessation, increased coherence in the theta band (within the hippocampus, amygdala and cortex) and brainstem feedbacks with the forebrain (Tsoukalas, 2012). ...
... "We are such stuff as dreams are made on, and our little life is rounded with a sleep." William Shakespeare 1.3 REM sleep is a sleep phase common to mammals and birds (i.e., homeothermic animals) characterized by random eye movements, generalized muscle atonia and, in the case of humans, frequent report of vivid dreams upon awakening (around 80% of times, although dreaming activity also occurs during NREM sleep), although it is generally thought that animals exhibiting REM sleep may also dream, albeit in a very different way than humans (Siegel, 2005, Tsoukalas, 2012, Siclari et al., 2014. REM sleep is sometimes also referred as paradoxical sleep due to some shared biological aspects with wakefulness, most notably, low amplitude and fast frequency brain waves in the electroencephalogram, high level of brain activity (particularly in the visual cortex, motor cortex and limbic system) and other hormonal similarities (e.g., in the cortisol levels) (Jones, 2016). ...
... Several studies indicate that the pons (located in the brainstem) is both necessary and sufficient for the generation of REM sleep (Tsoukalas, 2012). Impairment or damage in the frontal lobe might suppress dreaming, but does not interfere with REM activity itself (Siegel, 2011). ...
... Increased REM sleep also occurs when animals are immersed in an enriched environment, although the same holds for SWS (Rasch and Born, 2013). A second theory states that REM sleep evolved out of the tonic immobility reflex (a defense mechanism against predators based on death feigning, also known as animal hypnosis), as it is suggested by numerous biological similarities: low muscle tone, thermoregulatory cessation, increased coherence in the theta band (within the hippocampus, amygdala and cortex) and brainstem feedbacks with the forebrain (Tsoukalas, 2012). ...
Thesis
Full-text available
Rigorous study of effective connectivity and current source density underlying the sleep onset transition through a source localization tool (LORETA). It involves two conditions (baseline and recovery), which are also compared, showing the effects of increased sleep homeostatic load. The process is tracked as a function of time with all relevant statistical analysis. The study shows the prominent role of the default mode network and a causal mechanism located in the posteromedial cortex (posterior cingulate cortex/precuneus).
... This raises the question as to what kind of relationship REM sleep has to the central tenet of our thesis, namely that ToM evolved from a set of defensive reactions. An answer to this question is offered by a recent study which claims that REM sleep evolved out of the tonic immobility reflex (Tsoukalas 2012). This claim is based on the fact that REM sleep shows striking similarities-on both neurophysiological, phenomenological, and behavioral accounts-to this ancient defense mechanism. ...
... The answer favored here is that the reorganization of the mammalian brain gradually absorbed this primitive reflex and made it an integral part of its structure and function. 50 As new neural structures emerged around the TI module, its various components (inhibition, visual vigilance etc.) started to uncouple from each other and became embedded in different limbic and cortical circuits: one part leading to the postural atonia of REM sleep (Tsoukalas 2012), another leading to the transport reflex (Prestrude 1977;Webster et al. 1981;Meyer et al. 1984), and yet another becoming a contributor in the formation of the behavioral inhibition system or BIS (Gray 1982: 480-481). 51 In humans, this process went even further and eventually gave rise to such higher order capabilities as sustained attention and suggestibility (Cortez and Silva 2013), guilt and shame (Bovin et al., 2014), reflective thinking (Patterson & Newman, 1993;Erhard et al., 1999), parentchild attachment (Porges 2003) and the intentionality detector of ToM (Baron- Cohen 1995). ...
Article
Full-text available
Theory of mind is an important mental faculty. However, despite almost half a century of research, we only have a limited understanding of its evolutionary past. The present article proposes a novel hypothesis on the origin of this unique human capacity. According to this hypothesis theory of mind descended from two, closely related, defensive reactions, namely tonic immobility and immobilization stress. Both reactions are conserved in many vertebrate species and are highly prevalent in immature individuals. They are produced by a combination of manual handling and restraint (common in many nursing activities) and implicated in the management of stressful encounters. Most importantly, they have been shown to facilitate eye-contact, gaze-following, and intentional attributions. These traits, and several others detailed in the text, make them prime candidates in the search for the origin of theory of mind. The article presents conceptual arguments and empirical facts in support of this hypothesis.
... In nature, TI, also known as "immobility response", "immobility reflex", "animal hypnosis", "death feigning", and "behavioral arrest" (Carli et al., 1976;Klemm, 2001;Sandoval-Herrera et al., 2011), can be practically elicited in every animal species by a wide variety of stimuli (e.g., visual, auditory, olfactory, and tactile) (Klemm, 2001;Miranda-Páez et al., 2016). TI can be induced by injecting MLT in several animal species that become more susceptible to TI at night (Tsoukolas, 2012). Both antinociception and immobility are the main components of defensive reaction involving the PAG as one of the major centers. ...
... Another explanation could be that MLT needs the activation of the β-endorphin system by nociceptive stimuli to affect TI duration through microinjection into the D-PAG or VL-PAG. However, TI can be induced by systemic injection of MLT in several animal species, and MLT production can increase when these animals are exposed to stress or aggression (Tsoukolas, 2012). Furthermore, it has been observed that TI is more prolonged in stressed animals, and systemic injection of corticosterone also potentiates this behavior during stressful situations. ...
Article
Melatonin (MLT) is a neurohormone with significant involvement in several biological functions, of which antinociception and tonic immobility (TI) may be the key neurobehavioral components to survive in adverse conditions such as a predator attack. TI-induced antinociception can be elicited, facilitated, or increased through opioid and γ-aminobutyric acid (GABA) among other chemical mediators at several levels of the central nervous system, mainly in the periaqueductal gray (PAG). The aim of this study was to assess the effect of the microinjection of MLT into the main PAG regions that are related to different integrated defensive responses, namely dorsal (D) and ventrolateral (VL), on both antinociception through the tail-flick (TF) test and TI duration as single behavioral response and on combined behavioral responses (TF/TI). We found that the microinjection of MLT into the main PAG areas produced antinociception but did not affect the TI duration. The microinjection of MLT into the D-PAG decreased TF latency during TI in the combined trial (TF/TI), which implies that TI-induced antinociception was blocked. The microinjection of MLT into the VL-PAG maintained the antinociceptive capability of the TI without addition or increase in the antinociceptive effects, implying a permissive effect by MLT on the TI-induced antinociception. MLT administration into the D-PAG decreased the TI duration on the TF/TI, whereas MLT administration into the VL-PAG had the opposite effect of significantly increasing TI duration with the TF/TI trial.
... Internal browse of eyes may happen in two situations: a) Subconscious during awake when eyes are open, close, or blinking for thinking, memory access, and attention switching, respectively; b) Unconscious during sleep when eyes are closed such as in REM sleep for internal memory browse (Aserinsky and Kleitman, 1953;Tsoukalas, 2012). The fourth mode of eye movements will be formally analyzed in Section 3. ...
... In general, REM sleep accounts for 10-25% of sleep time as shown in Figure 3. However, NREM sleep takes 75-90% of sleep time where about 3-5% in Stage I, 50-60% in Stage II, and 10-20% in Stages III and IV, respectively (Hobson, 2009;Tsoukalas, 2012). REM sleep is characterized by three physiologic signs: a) Rapid eye movements; b) Muscle atonia; and c) Electroencephalograph (EEG) desynchronization (Aserinsky and Kleitman, 1953;Smith, 1993;Sternberg, 1998). ...
Article
Full-text available
Eyes as the unique organ possess intensively direct connections to the brain and dynamically perceptual accessibility to the mind. This paper analyzes the cognitive mechanisms of eyes not only as the sensory of vision, but also the browser of internal memory in thinking and perception. The browse function of eyes is created by abstract conditioning of the eye's tracking pathway for accessing internal memories, which enables eye movements to function as the driver of the perceptive thinking engine of the brain. The dual mechanisms of the eyes as both the external sensor of the brain and the internal browser of the mind are explained based on evidences and cognitive experiences in cognitive informatics, neuropsychology, cognitive science, and brain science. The finding on the experiment's internal browsing mechanism of eyes reveals a crucial role of eyes interacting with the brain for accessing internal memory and the cognitive knowledge base in thinking, perception, attention, consciousness, learning, memorization, and inference.
... So REM immobility could serve to reduce the chances of being attacked by a carnivorous predator. In this vein, Tsoukalas (2012) has proposed a theory that REM sleep has its origins in tonic immobility in animals. Importantly, REM atonia reduces the chances of acting out one's REM-related dreams and thus attracting the attention of nocturnal predators or disturbing the sleep of those around us. ...
Article
Full-text available
Sleep is a behavioral state whose quantity and quality represent a trade-off between the costs and benefits this state provides versus the costs and benefits of wakefulness. Like many species, we humans are particularly vulnerable during sleep because of our reduced ability to monitor the external environment for nighttime predators and other environmental dangers. A number of variations in sleep characteristics may have evolved over the course of human history to reduce this vulnerability, at both the individual and group level. The goals of this interdisciplinary review paper are (1) to explore a number of biological/instinctual features of sleep that may have adaptive utility in terms of enhancing the detection of external threats, and (2) to consider relatively recent cultural developments that improve vigilance and reduce vulnerability during sleep and the nighttime. This paper will also discuss possible benefits of the proposed adaptations beyond vigilance, as well as the potential costs associated with each of these proposed adaptations. Finally, testable hypotheses will be presented to evaluate the validity of these proposed adaptations.
... Behavioral inactivity during sleep can be compared to tonic immobility, a widespread form of adaptive behavior that feigns death in the face of danger (Overeem et al., 2002). Shared mechanisms have even been proposed for tonic immobility and REM sleep, which are both characterized by muscular atonia (Tsoukalas, 2012). Thus, immobility may help to escape predation (Meddis, 1975). ...
Thesis
Sleep is a mystery for the conscious mind. Indeed, whilst being asleep, either consciousness is reduced and few memories remain upon awakening. Or consciousness is altered during dreams and memories struck us by their incongruity. What happens then when we sleep? In this thesis, we played complex sounds to study how the brain interprets information from the external world during sleep. We asked ourselves how the sleep disconnection from its sensory environment depends on cognitive processes occurring during sleep. To do so, we used EEG, a brain imaging technique. We could show that the sleeping brain keeps on monitoring sounds and can even selectively enhance or suppress certain information, as well as learn a foreign language. These capacities depend nevertheless crucially on markers of internal activity during sleep, demonstrating that sleep is a fundamentally active process and host of complex cognitive [activity].
... REM is the simulation of death-feigning. According to Tsoukalas [101], REM sleep is a simulation of death-feigning as the last line of defense against an attacking predator by the total immobilization of the animal. The neurophysiology ...
... Carl Jung, the founder of analytical psychology, expanded on Freud's idea that dream content relates to the dreamer's unconscious desires 5 . Neurologists and neuroscientists explain dreams through different theories such as excitation of long-term memoriesor strengthening of semantic memories [6][7][8][9][10][11][12][13][14][15][16][17] . ...
... Acetylcholine is one of the main neurotransmitters of the central nervous system and plays a central role in cortical activation, behavioral inhibition, attention, memory and learning processes (Hasselmo, 2006;Kuo et al., 2007;Botly & de Rosa, 2008). The cholinergic circuits of the brainstem are also responsible for the production and control of REM sleep and hence play a crucial role in the regulation of the sleep-wake cycle (Hobson 1999;Tsoukalas 2012). Acetylcholine is the exclusive neurotransmitter of the parasympathetic nervous system, the part of the autonomic nervous system that is responsible for digestion, rest, recuperation and reproduction (McCorry, 2007). ...
Article
Full-text available
The present article is concerned with some aspects of lecithin metabolism and function as they pertain to mental health. Given that lecithin is a popular emulsifier in the food industry, as well as an active substance in many supplement formulations, its effects on mental health deserve special attention from a public health perspective. In this regard it is worrisome that a number of scientific studies, both old and new, have implicated the overconsumption of choline (a main ingredient of lecithin) in the causation of depression. The article discusses some of these concerns and proposes simple remedies.
... tonic immobility, a widespread response to predators among vertebrates and invertebrates). According to one recent hypothesis, REM sleep-with its associated paralysis-may have its roots in tonic immobility [114]. Researchers have identified neurological similarities between the paralysis in narcolepsy and tonic immobility in animals [115]. ...
Article
Full-text available
Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep - i.e., why sleep evolved - remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalian sleep to better understand sleep along the human lineage and in the modern world. Compared to other primates, sleep in great apes has undergone substantial evolutionary change, with all great apes building a sleeping platform or "nest." Further evolutionary change characterizes human sleep, with humans having the shortest sleep duration, yet the highest proportion of rapid eye movement (REM) sleep among primates. These changes likely reflect that our ancestors experienced fitness benefits from being active for a greater portion of the 24-hour cycle than other primates, potentially related to advantages arising from learning, socializing, and defending against predators and hostile conspecifics. Perspectives from evolutionary medicine have implications for understanding sleep disorders; we consider these perspectives in the context of insomnia, narcolepsy, seasonal affective disorder, circadian rhythm disorders, and sleep apnea. We also identify how human sleep today differs from sleep through most of human evolution, and the implications of these changes for global health and health disparities. More generally, our review highlights the importance of phylogenetic comparisons in understanding human health, including well-known links between sleep, cognitive performance and health in humans.
... The REM sleep has tonic and phasic components to characterize its influence on sleep. The phasic part of rapid eye movement sleep has been identified as a sympathetically driven state, which characteristically consists of rapid eye movements as well as respiratory variability and muscle twitches [4]. During REM, the tonic phase is the para-sympathetically driven phase and there is no eye movement; the length and density of the eye movement in REM period increases throughout the sleep cycle. ...
Article
Sleep is an important component of human life, yet many people do not understand the relationship between the brain and the process of sleeping. Sleep has been proven to improve memory recall, regulate metabolism, and reduce mental fatigue. A minimum of 7 hours of daily sleep seems to be necessary for proper cognitive and behavioral function. The emotional and mental handicaps associated with chronic sleep loss as well as the highly hazardous situations which can be contributed to the lack of sleep is a serious concern that people need to be aware of. When one sleeps, the brain reorganizes and recharges itself, and removes toxic waste byproducts which have accumulated throughout the day. This evidence demonstrates that sleeping can clear the brain and help maintain its normal functioning. Multiple studies have been done to determine the effects of total sleep deprivation; more recently some have been conducted to show the effects of sleep restriction, which is a much more common occurrence, have the same effects as total sleep deprivation. Each phase of the sleep cycle restores and rejuvenates the brain for optimal function. When sleep is deprived, the active process of the glymphatic system does not have time to perform that function, so toxins can build up, and the effects will become apparent in cognitive abilities, behavior, and judgment. As a background for this paper we have reviewed literature and research of sleep phases, effects of sleep deprivation, and the glymphatic system of the brain and its restorative effect during the sleep cycle.
Chapter
This chapter summarizes the main neurophysiological characteristics of tonic immobility (TI), in many susceptible species of mammals and birds. During TI, cortical EEG shows high voltage slow waves whose amount is affected by events preceding TI induction and is positively correlated with TI duration. The pattern of hippocampal activity helps to predict TI onset and TI termination. Both polysynaptic flexor and monosynaptic heteronymous reflexes are depressed independently from the EEG activity. Brain metabolism, signaled by glycogen mobilization and glucose utilization, indicates a reduced neuronal activity during TI. Learned avoidance responses to shock can be extinguished during TI and recover after TI. Moreover, during TI animals may learn how to avoid the shock by a motor response that may be followed by TI interruption. Decortication, decerebellation and telencephalic sections do not affect TI characteristics, whereas ponto-mesencephalic sections abolish both righting reflexes and TI.
Book
Full-text available
本书简述了大脑、神经系统及其演化,特别是视觉的原理及视觉系统的演化,重点论述了大脑的核心过程—学习、记忆、梦和意识,以及人的由来等问题。很多人相信视觉信息需要编码,提出的各种假说令人眼花缭乱—发放频率编码假说、同步振荡假说、时间编码假说、神经细胞集群假说、基本图形假设、稀疏和粗编码假说,等等,但作者认为,视觉过程并不需要任何编码与解码,也不存在压缩与解压缩,因此提出了视觉信息的非编码二步式并行传输模型,还提出了记忆模块学说,可以很好地诠释人类的记忆特征、我们为何做梦以及梦的特征,亦与记忆分子的标记、记忆归档、心理加工等证据相吻合。从进化上来看,记忆模块可满足对动态环境的适应需要,亦可满足快速决策的需要。 本书兼顾专业性与科普性,可供对此感兴趣的社会大众参考,在专业领域,可供医学、脑科学、神经生物学、人工智能、心理学、教育学、人类学、社会科学、考古学、基础生物学、生理学、动物行为学、进化生物学、生物化学、生物物理学、哲学等领域的科研人员及师生参考。
Preprint
Full-text available
Neurocognitive Processes of Hypnosis and Sleep
Article
Sleep disorders of all kinds are extremely frequent, in particular, insomnia, which affects 30%–40% of the population. Inadequate treatment of insomnia can easily transform an occasional poor sleeper into a patient with chronic insomnia, who, quite often, will become dependent on the regular use of medication. Obviously, the long-term health hazards of pharmaceuticals for treating sleep disorders are greatly ignored, as most have been on the market for only a few years. It is, therefore, urgent to propose an integrative and holistic approach to sleep-related problems. Although acupuncture has proven its efficiency for treating insomnia, unfortunately, most clinicians revert to standard “recipe-type” point combinations rather than designing personalized treatments for their patients. In Classical Chinese Medicine (CCM), the inner synchronizers that help patients to adapt to outer changes are the Eight Extraordinary Channels. A comprehensive approach based on the diagnosis of these channels can be an excellent option for developing individualized acupuncture treatments for patients. Western neurohumoral theories and discoveries about sleep are detailed and compared with classical Chinese concepts to deepen the understanding of the energetic aspects of sleep. Finally, a more effective acupuncture treatment approach is proposed. A proper diagnosis of insomnia based on CCM principles increases the efficiency, and reduces the number and duration, of acupuncture treatments.
Article
This article offers a holistic evolutionary perspective on dreaming and early sexual development. Going beyond Freud, and more in line with recent psychoanalysis and academic research, oedipality becomes part of understanding the development of sexual strategy, while dreaming is viewed as an evolved mechanism for moderating and updating affectively charged approach-avoidance conflicts associated with self-preservation and reproduction. The article suggests plausible evolutionary assumptions for interpretations of politics and expressive culture.
Article
Full-text available
Reviews data from a series of studies designed to test the hypothesis that tonic immobility (TI) represents an innate fear-potentiated response. In experiments using mostly 3–4 wk old Production Red chickens, fear was operationally defined by behavioral changes associated with long immobility reactions (i.e., defecation) and by certain manipulations, including (a) tranquilization, (b) intense auditory stimulation, (c) punishment, and (d) predatory confrontation with live and simulated stimuli, artificial eyes, and a visual cliff. Findings suggest that fear, while not the cause of TI, is an important antecedent condition for manipulating response duration and susceptibility. (61 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Full-text available
Reviews data that establish the importance of tonic immobility (TI) as a behavior which, at least in certain species, is functional in defense against predation. It is argued that the term "contact defense immobility" (CDI) would better distinguish this form of immobility from other types of behavioral arrest. Research dealing with the effect of various limbic lesions on CDI in the rabbit is examined, and several conclusions are drawn concerning response modulation by portions of the limbic system. In emphasizing the potential value of CDI in the study of brain/behavior relationships, it is noted that as the phenomenon exemplifies a functional, quantifiable emotional behavior with considerable species generality, it could be used as a model in which to make cross-species comparisons of the physiological correlates of fear. (45 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Full-text available
1. The brain has always played an important role in human evolution, but if brain size alone is the single neural variable considered, we cannot understand either the richness, complexity, or challenges inherent in a theory of human evolution. The brain is not simply a terminal product in mosaic human evolution.
Article
Full-text available
Melatonin, a hormone principally produced and released by the pineal gland, has been shown to regulate a variety of biological functions including circadian rhythms, sleep-wake cycles and reproduction1, presumably through activating high-affinity G-protein-coupled receptors2, 3, 4, 5. We report here that these subtypes can differentially modulate the function of type-A -aminobutyric acid (GABAA) receptor, the principal neurotransmitter receptor mediating synaptic inhibition in the CNS6, 7. This work demonstrates that melatonin, through activation of different receptor subtypes, can exert opposite effects on the same substrate, suggesting that receptor subtype is the primary molecular basis for the diversity of melatonin effects.
Article
Full-text available
Reviews research concerning hypnosis (tonic immobility) by inversion in the rabbit with respect to (a) brain activity, (b) motor response, (c) blood pressure and heart rate, (d) susceptibility and duration, (e) hormonal correlates, (f) learning and performance. Results obtained by using other methods to induce immobility, such as rotation and pressure, are also considered. Findings suggest that hypnosis in the rabbit represents a particular state of excitement in the CNS during which the motor system is affected by a tonic inhibitory influence which depresses spinal reflexes and prevents active movements. (3½ p ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Full-text available
Orexin (hypocretin) neurons, located exclusively in the PeF-LH, which includes the perifornical area (PeF), the lateral hypothalamus (LH), and lateral portions of the medial hypothalamus, have widespread projections and influence many physiological functions, including the autonomic regulation of body temperature and energy metabolism. Narcolepsy is characterized by the loss of orexin neurons and by disrupted sleep, but also by dysregulation of body temperature and by a strong tendency for obesity. Heat production (thermogenesis) in brown adipose tissue (BAT) contributes to the maintenance of body temperature and, through energy consumption, to body weight regulation. We identified a neural substrate for the influence of orexin neurons on BAT thermogenesis in rat. Nanoinjection of orexin-A (12 pmol) into the rostral raphe pallidus (rRPa), the site of BAT sympathetic premotor neurons, produced large, sustained increases in BAT sympathetic outflow and in BAT thermogenesis. Activation of neurons in the PeF-LH also enhanced BAT thermogenesis over a long time course. Combining viral retrograde tracing from BAT, or cholera toxin subunit b tracing from rRPa, with orexin immunohistochemistry revealed synaptic connections to BAT from orexin neurons in PeF-LH and from rRPa neurons with closely apposed, varicose orexin fibers, as well as a direct, orexinergic projection from PeF-LH to rRPa. These results indicate a potent modulation of BAT thermogenesis by orexin released from the terminals of orexin neurons in PeF-LH directly into the rRPa and provide a potential mechanism contributing to the disrupted regulation of body temperature and energy metabolism in the absence of orexin.
Article
Full-text available
Orexin A (OXA) modulates body weight, food intake and energy expenditure. In vitro, OXA increases PPARγ (also known as PPARG) expression and inhibits lipolysis, suggesting direct regulation of lipid metabolism. Here, we characterise the metabolic effects and mechanisms of OXA action in adipocytes. Isolated rat adipocytes and differentiated murine 3T3-L1 adipocytes were exposed to OXA in the presence or absence of phosphoinositide 3-kinase (PI3K) inhibitors. Pparγ expression was silenced using small interfering RNA. Glucose uptake, GLUT4 translocation, phosphatidylinositol (3,4,5)-trisphosphate production, lipogenesis, lipolysis, and adiponectin secretion were measured. Adiponectin plasma levels were determined in rats treated with OXA for 4 weeks. OXA PI3K-dependently stimulated active glucose uptake by translocating the glucose transporter GLUT4 from cytoplasm into the plasma membrane. OXA increased cellular triacylglycerol content via PI3K. Cellular triacylglycerol accumulation resulted from increased lipogenesis as well as from a decrease of lipolysis. Adiponectin levels in chow- and high-fat diet-fed rats treated chronically with OXA were increased. OXA stimulated adiponectin expression and secretion in adipocytes. Both pharmacological blockade of peroxisome proliferator-activated receptor γ (PPARγ) activity or silencing Pparγ expression prevented OXA from stimulating triacylglycerol accumulation and adiponectin production. Our study demonstrates that OXA stimulates glucose uptake in adipocytes and that the evolved energy is stored as lipids. OXA increases lipogenesis, inhibits lipolysis and stimulates the secretion of adiponectin. These effects are conferred via PI3K and PPARγ2. Overall, OXA's effects on lipids and adiponectin secretion resemble that of insulin sensitisers, suggesting a potential relevance of this peptide in metabolic disorders.
Article
Full-text available
Acute stressors induce changes in numerous behavioral parameters through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Several important hormones in paraventricular nucleus of the hypothalamus (PVN) play the roles in these stress-induced reactions. Corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP) and corticosterone are considered as molecular markers for stress-induced grooming behavior. Oxytocin in PVN is an essential modulator for stress-induced antinociception. The clock gene, Per1, has been identified as an effecter response to the acute stresses, but its function in neuroendocrine stress systems remains unclear. In the present study we observed the alterations in grooming and nociceptive behaviors induced by acute immobilization stress in Per1 mutant mice and other genotypes (wild types and Per2 mutant). The results displayed that stress elicited a more robust effect on grooming behavior in Per1 mutant mice than in other genotypes. Subsequently, the obvious stress-induced antinociception was observed in the wild-type and Per2 mutant mice, however, in Per1 mutant, this antinociceptive effects were partially-reversed (mechanical sensitivity), or over-reversed to hyperalgesia (thermal sensitivity). The real-time qPCR results showed that in PVN, there were stress-induced up-regulations of Crh, Avp and c-fos in all of genotypes; moreover, the expression change of Crh in Per1 mutant mice was much larger than in others. Another hormonal gene, Oxt, was up-regulated induced by stress in wild-type and Per2 mutant but not in Per1 mutant. In addition, the stress significantly elevated the serum corticosterone levels without genotype-dependent differences, and accordingly the glucocorticoid receptor gene, Nr3c1, expressed with a similar pattern in PVN of all strains. Taken together, the present study indicated that in acute stress treated Per1 mutant mice, there are abnormal hormonal responses in PVN, correlating with the aberrant performance of stress-induced behaviors. Therefore, our findings suggest a novel functional role of Per1 in neuroendocrine stress system, which further participates in analgesic regulation.
Article
Full-text available
Past research has shown that 37% to 52% of sexual assault survivors report experiencing a set of peritraumatic responses, which include gross motor inhibition, analgesia, and fixed or unfocused staring. This response set closely resembles a set of unconditioned responses, collectively known as Tonic Immobility (TI). This study examined TI among childhood sexual abuse (CSA) survivors and its relation to PTSD symptomatology. Participants were 131 female college undergraduates who completed questionnaires assessing sexual abuse history, TI, and PTSD symptom severity. Results showed that TI partially mediated the relation between peritraumatic fear and overall PTSD symptom severity and completely mediated the relation between fear and the PTSD reexperiencing symptoms. Although peritraumatic fear is associated with TI, the mediation findings provide evidence for the notion that these responses are separate from one another. These results suggest that TI during CSA may play an important role in the subsequent PTSD symptomatology in adulthood.
Article
Full-text available
Complaints of memory difficulties are common among patients with epilepsy, particularly with temporal lobe epilepsy where memory-related brain structures are directly involved by seizure activity. However, the reason for these complaints is often unclear and patients frequently perform normally on standard neuropsychological tests of memory. In this article, we review the literature on three recently described and interrelated forms of memory impairment associated with epilepsy: (i) transient epileptic amnesia, in which the sole or main manifestation of seizures is recurrent episodes of amnesia; (ii) accelerated long-term forgetting, in which newly acquired memories fade over days to weeks and (iii) remote memory impairment, in which there is loss of memories for personal or public facts or events from the distant past. Accelerated long-term forgetting and remote memory impairment are common amongst patients with transient epileptic amnesia, but have been reported in other forms of epilepsy. Their presence goes undetected by standard memory tests and yet they can have a profound impact on patients' lives. They pose challenges to current theoretical models of memory. We discuss the evidence for each of these phenomena, as well as their possible pathophysiological bases, methodological difficulties in their investigation and their theoretical implications.
Article
Anecdotal reports suggest dreams become more vivid and bizarre while taking melatonin. However, the connection between melatonin and dream characteristics has not been empirically established. The present study investigated the effects of 6 mg of melatonin (versus a placebo) on dream bizarreness in twenty two college students (8 male, 14 female), ages 18-25. The experiment ran for two weeks in which participants received either melatonin or a placebo for six nights. Each morning, participants provided a narrative of their dreams and also used a 7-point scale to respond to 17 questions measuring aspects of dream bizarreness. Bizarreness ratings following melatonin nights were compared with those following placebo nights. It was hypothesized that ratings of dream bizarreness would be reliably higher following melatonin treatments and that women would show greater increases than men. The hypotheses were partially supported by significant results on several specific aspects of dream bizarreness, including 'transformations of objects' and 'overall transformations.' Patterns differed for males and females, indicating that melatonin may, indeed, impact dreaming characteristics and participants' sex must be considered when investigating such effects.
Article
Predation by captive red foxes (Vulpes fulva) on approximately 50 ducks comprised of five species was observed in tests conducted at the Northern Prairie Wildlife Research Center, Jamestown, North Dakota. Most ducks were attacked from a rear or lateral position and seized in the cervical or thoracic region. All birds became immobile (death-feigned) immediately when seized and with few exceptions remained motionless during prey-handling and for varying lengths of time thereafter. Initial death feints lasted from 20 sec to 14 min. Recovery was delayed by tactile, visual and, possibly, auditory cues from the foxes. Death-feigning birds appeared alert and often took advantage of escape opportunities. Twenty-nine birds survived initial capture and handling by the foxes. Naive foxes were wary of ducks during initial confrontations, but experienced foxes showed little hesitation in attacking them. After capture, most ducks were taken alive to lay-down sites where they were mouthed and often killed. Then the ducks were usually cached or taken to dens or pups. Several birds were cached alive. Red foxes appear to have adapted to the escape of death-feigning ducks by learning to kill some birds soon after capture and by the evolution of an appendage-severing behavior. Death feigning appears to be a highly developed antipredator behavior of ducks that facilitates the escape of some birds after capture by red foxes.
Article
Abstract We hypothesized that representations of social interactions in REM and non-REM (NREM) dreams would reflect differing regional brain activation patterns associated with the two sleep states, and that levels of aggressive interactions would be higher in REM than in NREM dreams. One hundred REM, 100 NREM, and 100 wake reports were collected in the home from 8 men and 7 women using the Nightcap sleep-wake mentation-monitoring system and scored for number and variety of social interactions. We found that (a) social interactions were more likely to be depicted in dream than in wake reports, (b) aggressive social interactions were more characteristic of REM than NREM or wake reports, and (c) dreamer-initiated friendliness was more characteristic of NREM than REM reports. We conclude that processing of, or simulations about, selected social interactions is preferentially performed while “off-line” during the dream state, with the REM state specializing in simulation of aggressive interactions and the NREM state specializing in simulation of friendly interactions.
Article
Serotonin (5-HT) participates as a neurotransmitter in the control of the circadian sleep/wake rhythm, feeding and sexual behaviours, and emotional and affective states. The present study investigated whether melatonin affects the circadian rhythm of 5-HT neurotransmission in the hippocampus, a major target for serotoninergic antidepressants. The present results show a daytime dependency of [3H]5-HT uptake insensitive to melatonin, with a peak from 14.00 h to 22.00 h and a trough from 02.00 h to 06.00 h. They also indicate that melatonin reduced the spontaneous efflux of [3H]5-HT as well as KCI-evoked release of [3H]5-HT during the dark phase, while it increased the evoked release during the light phase. Both effects were concentration-dependent; the facilitatory effect was maximum at high nanomolar concentrations of melatonin, whereas the inhibition preferentially occurred at low concentrations. Finally, nifedipine, an effective antagonist of L-type voltage-sensitive calcium channels, prevented the effects of melatonin on KCI-evoked [3H]5-HT release during the light but not the dark phase. Together, these data suggest the involvement of two distinct mechanisms by which melatonin might regulate both spontaneous efflux and evoked release of 5-HT in the hippocampus.
Article
Mice of C57BL/6J strain were exposed to trained fighters twice a day for 0 (not fought controls), 2, 4, 8 and 16 days. Twenty min after the last fight, the mice were killed, and the hypothalamus, amygdala and frontal cortex removed, frozen, weighed and kept frozen until analyzed fluorimetrically for the content of serotonin and norepinephrine. The maximum storage time at −30°C never exceeded 4 weeks. Results indicate that after an initial decline in hypothalamic and amygdaloid level of serotonin, there followed a significant rise in this amine during the remaining period of 16 days of exposure to aggression and defeat. However, the frontal cortical levels of serotonin exhibited a continual decline in serotonin from a control level of 0.64 to a level of 0.38 μg/g after 16 days of daily exposure to this treatment. The level of norepinephrine in the amygdala and hypothalamus exhibited an initial rise, but thereafter declined significantly. Thus, at 16 days, the norepinephrine level in the amygdala was 0.306 and in the hypothalamus, the level was 0.876 μg/g. The initial control values for these areas were 0.66 and 1.215 μg/g, respectively. The norepinephrine level in the frontal cortex exhibited a progressive increase to 0.662 at 16 days from a control level of 0.306 μg/g. Generally, a reciprocal relationship existed between serotonin and norepinephrine supporting the ergotropic-trophotropic role attributed to these biogenic amines.
Article
We have investigated the role of ascending noradrenergic pathways in the control of oxytocin (OT) and arginine-vasopressin (AVP) secretion during acute immobilization stress in male and female rats. 6-Hydroxydopamine-induced lesions of the ventral noradrenergic bundle (VNAB) resulted in a selective depletion of hypothalamic noradrenaline content. In sham-lesioned rats plasma levels of OT were raised following stress, the response being significantly greater in female compared with male animals. VNAB lesions were not associated with altered responses in female rats, whereas lesioned males exhibited markedly elevated OT stress responses. AVP secretion was not modulated in VNAB-lesioned rats of either sex. The results provide functional evidence of a sexually dimorphic inhibitory role of the VNAB in the control of OT secretion.
Article
The effects of pinealectomy on paradoxical sleep (SP) and slow-wave sleep (SL) have been studied in rats maintained with a 12/12 light-dark schedule. Continuous recordings (24 h/day) from cerebral cortex and neck muscles were used to monitor SL, SP and arousal in the same 7 male rats during 8 days before and 30 days after pinealectomy. The technique of pinealectomy spares the venous sinuses and can be performed on already implanted rats. Following pinealectomy, a dissociation developed between the nyctohemeral variations of SP and SL. There were no changes in the amount of SP and SL on a 24-h base but SP decreased during the light phase of the cycle and increased during the dark phase. The diurnal variations in SL were normal. The circadian variations in SL remained as in control conditions with high spectrum values for a 24-h periodicity. In contrast to this the circadian periodicity of SP was almost abolished. Our data suggest that the pineal organ can play an important role in the diurnal and circadian organization of SP and its phase relationships with SL.
Article
BACKGROUND: Previous studies suggested the importance of peritraumatic reactions as predictors of PSTD symptoms severity. Despite mounting evidence that tonic immobility occurs under intense life threats its role as predictor of PTSD severity remains by and large understudied. The objective of this study was to investigate the role of peritraumatic reactions (tonic immobility, panic and dissociation) as predictors of PTSD symptoms severity. METHODS: Participants were 32 victims of urban violence with PTSD diagnosed through the SCID-I. In order to evaluate PTSD symptoms at baseline, we used the Post-Traumatic Stress Disorder Checklist-Civilian Version. To assess peritraumatic reactions we employed the Physical Reactions Scale, the Peritraumatic Dissociative Experiences Questionnaire and Tonic Immobility questions. As confounding variables, we considered negative affect (measured by the Positive and Negative Affect Schedule-Trait Version), sex and time elapsed since trauma. RESULTS: Tonic immobility was the only predictor of PTSD symptoms severity that kept the statistical significance after controlling for potential confounders. LIMITATIONS: This study was based on a relatively small sample recruited in a tertiary clinic, a fact that may limit the generalizability of its findings. The retrospective design may have predisposed to recall bias. CONCLUSIONS: Our study provides good reason to conduct more research on tonic immobility in PTSD with other samples and with different time frames in an attempt to replicate these stimulating results.
Article
In this article the authors propose, on the basis of a review of the evolutionary and neuropsychological study of REM sleep, that REM sleep functions to promote attachment and that in the mature state it may promote sexual pair bonding and serve related compensatory functions. The attachment hypothesis is consistent with known psychobiologic correlates of REM sleep, with classical psychoanalytic theory regarding dreams, and with evidence from research on attachment. The authors argue that this hypothesis leads to a new understanding of the role of repression and the dream work, and has broad implications for psychopathology research. They argue that although many in the cognitive and neural sciences have largely dismissed S. Freud's (1900/1953) theorizing on dreams, there is important complementarity when it is evaluated through the lens of the attachment hypothesis. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
A review of literature indicates that so many conspicuous differences exist among the responses subsumed under the term "animal hypnosis" that a unitary approach to the phenomena may be a misleading oversimplification. Six response differences are distinguished and, using the immobility response produced by inversion and restriction as a reference point, are compared with respect to stimulus characteristics, response characteristics, neural control mechanisms, physiological correlates, and species specificity. It is argued that by emphasizing response differences, it may be possible to avoid some problems inherent in the unitary approach, such as the tendency to postulate a common function for immobility responses. (38 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
The neurohypophysial hormones oxytocin and vasopressin show daily rhythms of secretion with elevated hormone release during the hours of sleep. This pattern can be modulated by ovarian steroids and alters with age. The pattern appears to be due in part to the nocturnal increase in melatonin secretion, which stimulates hormone release in man, while being inhibitory in the rat. Pinealectomy alters both the 24 h pattern of neurohypophysial hormone release in the rat and the firing rate of magnocellular supraoptic nucleus neurones. There is also a reduced hormone release in response to hypovolaemia and raised plasma sodium concentration compared to sham operated animals, with a smaller increase in neuronal activity, as determined by immediate-early gene expression. The normal responses can be restored by nocturnal administration of melatonin. Melatonin also influences the neurohypophysial hormone response in the human to known stimuli of release, such as raised plasma osmolality, exercise and insulin-induced hypoglycaemia. Recent studies have revealed that not only does the release of vasopressin and oxytocin vary over each 24 h, but the respective renal and pregnant uterine responses also show diurnal variations.
Article
Tonic immobility and several accompanying behavioral changes were examined in the squirrel monkey (Saimiri sciureus). It was found that either the occurrence of a loud noise immediately before induction or the presence of a stuffed Cooper's hawk increased the duration of immobility in some subjects. Subspecies differences in durations of immobility were also found. The number of inductions required to produce immobility in squirrel monkeys were unusually large, and were negatively correlated with duration of the response. Behavioral variables accompanying tonic immobility showed qualitative differences when compared to what is known concerning their relation to immobility in other species. The findings support the belief that tonic immobility evolved as a predator defense in squirrel monkeys or one of their ancestors, but suggest that it no longer plays an active role in their survival.
Article
Circadian rhythms of tonic immobility were found in male albino rats raised on a 12-h diurnal light cycle and tested at 6-h intervals. Durations of immobility were twice as long at 2000 h as at 1400 h. These differences persisted when rats were exposed to constant darkness for 10 days, but disappeared when rats were maintained in constant light for the same period. Since endogenous circadian rhythms of certain monoamine levels persist in constant darkness yet disappear under constant light, it is suggested that cycles of tonic immobility in rats are also endogenous. When the diurnal pattern of tonic immobility duration is compared to that of various neurohumors, immobility duration appears to parallel melatonin production and to be opposite in phase to the cycle of serotonin levels. Duration of immobility increased over trials, although the number of inductions required to produce immobility decreased. This suggests that instrumental conditioning may modify the immobility response to some extent.
Article
The effect of tonic immobility on serotonin (5-hydroxytryptamine, 5-HT) and on 5-hydroxyindolacetic acid (5-HIAA) levels in different brain areas has been investigated, following two different schedules of treatment. The massed treatment consisted of a series of consecutive trials up to 15 min, the spaced treatment in 4 series of trials within 24 hours. Massed treatment produced a decrease in 5-HT in the mesencephalon and of 5-HIAA in the pons-medullary area, but similar changes were also elicited in animals treated with the procedure of induction not followed by immobility. The spaced treatment, which resulted in a potentiation of the immobility duration, i.e., sensitization, produced a reduction of 5-HT levels in the mesencephalon and of 5-HT turnover in the striatum. The procedure of the induction per se acts preferentially on 5-HIAA by increasing its levels. In the striatum, which appears selectively responsive to the spaced treatment of immobility, a negative correlation has been found between serotonin levels and immobility duration. Results suggest that elicitation of tonic immobility is associated with reduced levels of 5-HT in the brain.
Article
Previous studies have implicated a serotonergic neurochemical system in the control of tonic immobility. The present study examined the effects on immobility of peripheral injections of chemicals found in the various stages of serotonin synthesis and metabolism. Anoles (Anolis carolinensis) were selected to study because certain of these substances produce skin color changes in the anole, affording a check on the efficacy of the chemicals administered. Although tryptophan produced no significant changes, 5-hydroxytryptophan darkened the anole's skin and decreased the number of inductions required to produce tonic immobility. Serotonin also darkened the anole's skin, but produced little change in immobility. 5-Hydroxyindole acetic acid, N-acetylserotonin, and melatonin all significantly lengthened durations of tonic immobility and lightened skin color, and melatonin had the most profound effects on both. These findings suggest that the metabolic byproducts of serotonin, melatonin and 5-hydroxyindole acetic acid, may play a crucial role in the neurochemical control of tonic immobility.
Article
Infant rats aged 1 to 5 days lose heat rapidly when first exposed to room temperature; they also are initially very active and cannot be immobilized when turned over onto their sides and restrained for a few seconds. However, once core temperature drops closer to ambient levels, the stimulus for movement (rapid loss of heat from skin to environment) is diminished and immobility occurs. If the rapid heat loss, a source of apparent spontaneity, is prevented by precooling or continuous warmth, activity is blocked and prolonged restraint-related immobility can be readily produced. The warmed pups frequently made small twitches typical of those associated with paradoxical sleep. By 10 days, the pups can no longer be immobilized on their sides when pre-cooled, possibly because motor subsystems related to shivering thermogenesis (i.e., behaviors, including righting, that actively maintained a crouched upright position) begin to develop. At this age the pups can still be immobilized when warmed, but by 25 days of age slight warming is no longer effective because of the emergence of other sources of spontaneous locomotion that cannot be blocked by warmth, and/or because warmth can no longer induce paradoxical sleep. To test for the influence of the developing neocortex on immobility, pups were decorticated at 6 days of age. The activity and restraint immobility durations of the decorticate pups were not different from controls under any thermal condition at any postoperative age. Warmth-induced immboility was present following decortication in adult rats, but only in the early postoperative days, perhaps relating to subcortical diaschisis. It is suggested that the neocortex is not a major inhibitory influence on immobility induced by restraint.
Article
Hippocampal electrical activity has been studied in 12 unanaesthetized, unrestrained rabbits during hypnosis and spontaneous activity in the experimental cage, before and among hypnosis trials. Quantitative analyses showed that rhythmic slow activity (RSA) occurred during exploratory movements (mean frequency 7.2 Hz) and also during spontaneous immobility, but at a lower percentage and frequency (6.5 Hz). RSA was always present during the induction of hypnosis, but its frequency decreased and disappeared at the beginning of immobility, when it was replaced by a large amplitude irregular activity (LIA). During hypnosis RSA occurred in short periods, at low frequency (5.7 Hz). During the initial part of hypnosis, the lowest percentage of RSA was recorded. In the second and third part, RSA increased in number of episodes, total amount, duration of a single episode and mean frequency. RSA of higher frequency occurred at the end of hypnosis, preceding righting movements. The relationships between hippocampal RSA and animal hypnosis are discussed.
Article
Research involving the effects of serotonergic and other pharmacological manipulations on tonic immobility is reviewed. An attempt is made to show how these findings parallel independent research involving precursor availability and drug-induced changes in the electrical activity of raphe neurons. Central serotonergic neuronal mechanisms appear to play a crucial role in modulating tonic immobility.
Article
Three experiments were conducted measuring within-animal changes in heart rate, respiration rate, and body temperature during tonic immobility. Following immobility onset, heart rate decreased and reached its lowest level just prior to response termination, respiration rate increased initially and then gradually decreased during the immobility episode, while body temperature remained lowered throughout the response period. The results were discussed in relation to the hypothesis that immobility might be related to an aversive emotional state.
Article
Brown adipocytes burn chemical energy to produce heat for protection against hypothermia and obesity. Sellayah et al. now reveal that a secreted neuropeptide, Orexin, functions a key driver of brown adipocyte differentiation through direct actions on brown adipose precursors.
Article
To further define the function of the oxytocin receptor (OXTR) in vivo, we generated mice deficient in the Oxtr gene (Oxtr-/-). Oxtr-/- mice had no obvious deficits in fertility or sexual behaviour, but displayed several aberrations in social behaviours, including male aggression, and mother-offspring interaction. In addition, they showed novel physiological defects including obesity, and dysfunction in body temperature control when exposed to cold. We review here our new findings with Oxtr-/- mice, and introduce newly generated Oxtr-Venus knockin mice as a potential tool for examining molecular physiology of Oxtr-neurons.
Article
Orexin neurons contribute to cardiovascular, respiratory and analgesic components of the fight-or-flight response against stressors. Here, we examined whether the same is true for stress-induced hyperthermia. We used prepro-orexin knockout mice (ORX-KO) and orexin neuron-ablated mice (ORX-AB) in which the latter lack not only orexin, but also other putative neurotransmitter/modulators contained in the orexin neurons. In response to repetitive insertion of a temperature probe into their rectum (handling stress), ORX-KO mice showed a normal temperature change as compared to that of wild-type littermates (WT) while ORX-AB showed an attenuated response. Stress-induced expression of uncoupling protein-1, a key molecule in non-shivering thermogenesis in the brown adipose tissue (BAT), was also blunted in ORX-AB but not in ORX-KO. When the BAT was directly activated by a β3 adrenergic agonist, there was no difference in the resultant BAT temperature among the groups, indicating that BAT per se was normal in ORX-AB. In WT and ORX-KO, handling stress activated orexin neurons (as revealed by increased expression of c-Fos) and the resultant hyperthermia was largely blunted by pre-treatment with a β3 antagonist. This observation further supports the notion that attenuated stress-induced hyperthermia in ORX-AB mice was caused by a loss of orexin neurons and abnormal BAT regulation. This study pointed out, for the first time, the possible importance of co-existent neurotransmitter/modulators in the orexin neurons for stress-induced hyperthermia and the importance of integrity of the orexin neurons for full expression of multiple facets of the fight-or-flight response.
Article
Tonic immobility is the last defense reaction to entrapment by a predator. In humans, peritraumatic tonic immobility was correlated with PTSD severity and poor response to treatment. This study compared the role of peritraumatic dissociation, panic physical symptoms and tonic immobility as predictors of response to standard pharmacotherapy for PTSD. Thirty-six PTSD patients underwent a naturalistic pharmacological treatment. The Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C) and the Clinical Global Impressions Severity of Illness item scores (CGI-S) were employed at baseline and endpoint to examine treatment outcome. Peritraumatic reactions were assessed using the Physical Reactions Subscale, the Peritraumatic Dissociative Experiences Questionnaire and four motor questions of the Tonic Immobility Scale. After controlling for confounders, tonic immobility was the best predictor of a poor response to treatment, either considering the PCL-C or the CGI-S scores. Tonic immobility seems to have a greater negative impact on PTSD prognosis than peritraumatic panic or dissociation. Additional translational and clinical research may inform about particular mechanisms underlying tonic immobility and open new avenues for prevention and treatment of PTSD.
Article
Tonic immobility (TI) is an innate defensive behavior characterized by a state of physical inactivity and diminished responsiveness to environmental stimuli. Behavioral adaptations to changes in the external and internal milieu involve complex neuronal network activity and a large number of chemical neurotransmitters. The TI response is thought to be influenced by serotonin (5-HT) activity in the central nervous system (CNS) of vertebrates, but the neuronal groups involved in the mechanisms underlying this behavior are poorly understood. Owing to its extensive afferents and efferents, the dorsal raphe nucleus (DRN) has been implicated in a great variety of physiological and behavioral functions. In the current study, we investigated the influence of serotonergic 5-HT(1A) and 5-HT(2) receptor activity within the DRN on the modulation of TI behavior in the guinea pig. Microinjection of a 5-HT(1A) receptor agonist (8-OH-DPAT, 0.01 and 0.1 microg) decreased TI behavior, an effect blocked by pretreatment with WAY-100635 (0.033 microg), a 5-HT(1A) antagonist. In contrast, activation of 5-HT(2) receptors within the DRN (alpha-methyl-5-HT, 0.5 microg) increased the TI duration, and this effect could be reversed by pretreatment with an ineffective dose (0.01 microg) of ketanserine. Since the 5-HT(1A) and 5-HT(2) agonists decreased and increased, respectively, the duration of TI, different serotonin receptor subtypes may play distinct roles in the modulation of TI in the guinea pig.
Article
The neuropeptide oxytocin is involved in the development and maintenance of attachment behaviours in humans and other species. Little is known, however, about how it affects judgements of unfamiliar others. In a double-blind placebo-controlled study we investigated the effect of a single intranasal dose of oxytocin on judgements of facial trustworthiness and attractiveness. We found that oxytocin administration increased ratings of trustworthiness and attractiveness of male and female targets in raters of both sexes relative to control ratings, suggesting that higher levels of this neuropeptide may enhance affiliative behaviour towards unfamiliar others. Our results provide evidence in support of a general facilitative role of oxytocin in promoting positive trait judgements.
Article
Tonic immobility (TI) is a temporary state of motor inhibition believed to be a response to situations involving extreme fear. Limited attention has been directed to studying TI in humans; however, the phenomenon has been well documented in the animal literature. In humans, TI is believed to occur during sexual assault, and there have been reports of fear-induced freezing in the contexts of air, naval, and other disasters. This study had three main purposes: (1) to assess the factor structure of a new self-report measure--the Tonic Immobility Questionnaire--designed to assess human TI in a range of traumatic events; (2) to explore associations among discovered TIQ factors and a measure of posttraumatic symptoms in the context of trauma type; and (3) to determine whether TI is related to suspected and empirically supported predictors of posttraumatic stress disorder. Participants were a subset of undergraduate students (n=78) who reported a TI experience in the context of a traumatic event. No differences were found in frequency or severity of TI reported across trauma types. Exploratory factor analysis of Tonic Immobility Questionnaire item responses resulted in a three-factor solution (i.e., physical immobility, fear, and dissociation). Significant positive correlations were found between the Tonic Immobility Questionnaire and measures of posttraumatic symptoms, dissociation, anxiety sensitivity, and absorption. Regression analysis revealed that peritraumatic dissociation scores alone accounted for 51% of the variance in TI scores. TI may represent an extreme behavioral expression of trauma-induced peritraumatic dissociation. Implications and directions for future research are discussed.
Article
Several physiological, pharmacological and behavioral lines of evidence suggest that the hippocampal formation is involved in nociception. The hippocampus is also believed to play an important role in the affective and motivational components of pain perception. Thus, our aim was to investigate the participation of cholinergic, opioidergic and GABAergic systems of the dorsal hippocampus (DH) in the modulation of nociception in guinea pigs. The test used consisted of the application of a peripheral noxious stimulus (electric shock) that provokes the emission of a vocalization response by the animal. Our results showed that, in guinea pigs, microinjection of carbachol, morphine and bicuculline into the DH promoted antinociception, while muscimol promoted pronociception. These results were verified by a decrease and an increase, respectively, in the vocalization index in the vocalization test. This antinociceptive effect of carbachol (2.7 nmol) was blocked by previous administration of atropine (0.7 nmol) or naloxone (1.3 nmol) into the same site. In addition, the decrease in the vocalization index induced by the microinjection of morphine (2.2 nmol) into the DH was prevented by pretreatment with naloxone (1.3 nmol) or muscimol (0.5 nmol). At doses of 1.0 nmol, muscimol microinjection caused pronociception, while bicuculline promoted antinociception. These results indicate the involvement of the cholinergic, opioidergic and GABAergic systems of the DH in the modulation of antinociception in guinea pigs. In addition, the present study suggests that cholinergic transmission may activate the release of endorphins/enkephalin from interneurons of the DH, which would inhibit GABAergic neurons, resulting in antinociception.
Article
Although opioids are known to influence sleep-wake regulation, the neuroanatomic substrate(s) mediating these effects remain unresolved. We hypothesized that the influence of opiates on sleep may be mediated, at least in part, by the ventrolateral preoptic nucleus (VLPO), a key cell group for producing behavioral sleep. By combining in situ hybridization for kappa and mu receptor mRNA with immunostaining of Fos expressed by VLPO cells during sleep we show that >85% of sleep-active VLPO neurons contain mRNA for either or both opioid receptors. Microinfusions of a kappa receptor agonist into the VLPO region increased NREM sleep by 51% during the subjective night, whereas a mu receptor agonist increased wakefulness by 60% during the subjective day. The sleep- and wake-promoting effects of the kappa and mu agonists were blocked by prior administration of their respective antagonist. Combining retrograde tracing from the VLPO with immunohistochemistry for dynorphin (Dyn, the endogenous kappa receptor agonist) or endomorphin 1 (EM1, the endogenous mu receptor agonist) we show that the central lateral parabrachial subnucleus (PBcl) provides Dyn inputs to the VLPO, whereas hypothalamic histaminergic neurons provide EM1 inputs to the VLPO. In summary, results from the present study suggest that central opioid inputs to the VLPO may play a role in sleep-wake regulation and that the VLPO likely mediates the hypnotic response to high levels of opioid analgesics.
Article
The tonic immobility state (TIS) in rabbit has great potential as an animal model of hypnosis in humans, due to the strong similarities between TIS and hypnosis. It is additionally the only mammalian model available for studying mechanisms of hypnosis. However, its ability to modulate pain perception has yet to be clearly determined. The present experiment examined the effect of nociceptive conditioning in normal, TIS and lidocaine-treated rabbits. This involved three separate phases. In phase one all animals were trained on a continuous performance test (CPT). In the second phase animals were given Pavlovian conditioning to an auditory CS paired with a nociceptive US. In the third phase the animals are given a sensory recognition test. The control group were conditioned during a normal state, the TIS group were conditioned during TIS, the pain control animals were conditioned after lidocaine injection in the skin area stimulated by the nociceptive US. All animals in the normal group showed the greatest amount of pain conditioning, with an average disruption time (dt) of 175s. Animals in the lidocaine group showed little signs of conditioning with an average dt of 16s. Animals conditioned during TIS had an average dt of 42s. These results show that TIS can modulate pain perception similar to animals that did not experience a pain CS. They additionally argue that tonic immobility can produce attenuation of pain perception similar to hypnosis in humans.
Article
Organisms must adapt to seasonal changes in the environment and time their physiology accordingly. In vertebrates, the annual change in photoperiod is often critical for entraining the neuroendocrine pathways, which drive seasonal metabolic and reproductive cycles. These cycles depend on thyroid hormone (TH), reflecting its ancestral role in metabolic control. Recent studies reveal that--in mammals and birds--TH effects are mediated by the hypothalamus. Photoperiodic manipulations alter hypothalamic TH availability by regulating the expression of TH deiodinases (DIO). In non-mammalian vertebrates, light acts through extraretinal, 'deep brain' photoreceptors, and the eyes are not involved in seasonal photoperiodic responses. In mammals, extraretinal photoreceptors have been lost, and the nocturnal melatonin signal generated from the pineal gland has been co-opted to provide the photoperiodic message. Pineal function is phased to the light-dark cycle by retinal input, and photoperiodic changes in melatonin secretion control neuroendocrine pathway function. New evidence indicates that these comparatively divergent photosensensory mechanisms re-converge in the pars tuberalis of the pituitary, lying beneath the hypothalamus. In all vertebrates studied, the pars tuberalis secretes thyrotrophin in a light- or melatonin-sensitive manner, to act on neighbouring hypothalamic DIO expressing cells. Hence, an ancient and fundamentally conserved brain thyroid signalling system governs seasonal biology in vertebrates.
Article
The brainstem reticular formation is an area important to the control of rapid eye movement (REM) sleep. The antagonist of GABA-type A (GABA(A)) receptors, bicuculline methiodide (BMI), injected into the rat nucleus pontis oralis (PnO) of the reticular formation resulted in a long-lasting increase in REM sleep. Thus, one factor controlling REM sleep appears to be the number of functional GABA(A) receptors in the PnO. The long-lasting effect produced by BMI may result from secondary influences on other neurotransmitter systems known to have long-lasting effects. To study this question, rats were surgically prepared for chronic sleep recording and additionally implanted with guide cannulas aimed at sites in the PnO. Multiple, 60 nl, unilateral injections were made either singly or in combination. GABA(A) receptor antagonists, BMI and gabazine (GBZ), produced dose-dependent increases in REM sleep with GBZ being approximately 35 times more potent than BMI. GBZ and the cholinergic agonist, carbachol, produced very similar results, both increasing REM sleep for about 8 h, mainly through increased period frequency, with little reduction in REM latency. Pre-injection of the muscarinic antagonist, atropine, completely blocked the REM sleep-increase by GBZ. GABAergic control of REM sleep in the PnO requires the cholinergic system and may be acting through presynaptic modulation of acetylcholine release.