REM sleep and memory

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Neural networks and REM sleep

The nature of certain forms of memory is discussed in relation to neural networks and REM sleep.     

Tyrosine hydroxylase activity in rat brain following "REM" sleep deprivation

I n R ecent years biogenic amines have been implicated in the control mechanism for induction and maintenance of sleep processes (J ouvet , 1969). Investigators have looked for changes in the rate of synthesis of cerebral norepinephrine from [³H]tyrosine after REM sleep deprivation and reported increased rates of synthesis during REM sleep deprivation (M ark , H einer , M andel and G odin , 1969) and REM sleep rebound following 91 h of deprivation (P ujol , M ouret and G lowinski , 1968). Because tyrosine is thought to be the rate-limiting enzyme (U denfriend , 1966) in the synthetic pathways for norepinephrine and since the above-mentioned studies are suggestive of changes in the activity of the enzyme, we decided to measure tyrosine hydroxylase activity following REM sleep deprivation.     

Ambient temperature-dependent thermoregulatory role of REM sleep

Changes in ambient temperature produce complex effects on sleep–wakefulness. In order to find out the mechanisms involved in temperature-sensitive changes in sleep in rats, their thermal preference, body temperature and sleep were studied before and after the destruction of both peripheral and central warm receptors, by systemic administration of 375 mg/kg capsaicin. Though the pre-treated rats preferred to stay mostly at the ambient temperature of 27 °C, post-treated rats strayed freely into chambers having ambient temperature of 30 °C and 33 °C. Sleep and body temperature of these rats were studied for six hours each, when they were kept at an ambient temperature of 18–36 °C. Total sleep time, especially REM sleep, was maximum at 30 °C in pre-treated rats, but this REM sleep peak at 30 °C disappeared after capsaicin administration. Body temperature increased sharply in post-treated rats, at ambient temperatures above 30 °C. Apart from the ability to defend body temperature at high ambient temperature, avoidance of warm ambient temperature and increase in REM sleep are the behavioral measures which are lost in post-treated rats. Results of this study suggest that the ambient temperature-related increase in REM sleep at 30 °C could be part of the thermoregulatory measures.     

Mechanisms and models of REM sleep control

The first sections of this paper survey the history and recent developments relevant to the major neurotransmitters and neuromodulators involved in REM sleep control. The last portion of this paper proposes a structural model of cellular interaction that produces the REM sleep cycle, and constitutes a further revision of the reciprocal interaction model This paper proposes seven criteria to define a causal role in REM sleep control for putative neuro-transmitters/modulators. The principal criteria are measurements during behavioral state changes of the extracellular concentrations of the putative substances, and electrophysiological recording of their neuronal source. A cautionary note is that, while pharmacological manipulations are suggestive, they alone do not provide definitive causal evidence. The extensive body of in vivo and in vitro evidence supporting cholinergic promotion of REM sleep via LDT/PPT neuronal activity is surveyed. An interesting question raised by some studies is whether cholinergic influences in rat are less puissant than in cat. At least some of the apparent lesser REM-inducing effect of carbachol in the rat may be due to incomplete control of circadian influences; almost all experiments have been run only in the daytime, inactive period, when REM sleep is more prominent, rather than in the REM-sparse nighttime inactive period. Monoaminergic inhibition of cholinergic neurons, once thought to be the most shaky proposal of the reciprocal interaction model, now enjoys considerable support from both in vivo and in vitro data. However, the observed time course of monoaminergic neurons, their "turning off" discharge activity as REM sleep is approached and entered would seem to be difficult to produce from feedback inhibition, as originally postulated by the reciprocal interaction model. New data suggest the possibility that GABAergic inhibition of Locus Coeruleus and Dorsal Raphe monoaminergic neurons may account for the "REM-off" neurons turning off. However, the source(s) of GABAergic influences suggested by anatomical studies has yet to be definitively identified by electrophysiological recordings of GABAergic neurons that show the requisite inverse time course of activity relative to monoaminergic neurons. New and still preliminary microdialysis data suggest that reticular formation neurons, the effector neurons for REM sleep phenomena, might be disinhibited during REM sleep by decreased GABAergic influence, perhaps stemming from REM-on cholinergic neuronal inhibition of reticular formation GABAergic neurons. Whether the postulated cholinergic inhibition of GABAergic neurons is present is testable with in vitro recordings and double labeling. Taking into account the observed data on neuro-modulators/transmitters, a structural model incorporating interaction of REM-on and REM-off neurons and GABAergic influences is proposed. Finally, with respect to orexin and REM sleep, it is hypothesized that orexinergic activity may be a principal factor controlling REM sleep's absence from the active period in strongly circadian animals such as rat and man.     

Neural-mechanical coupling of breathing in REM sleep

Smith, C. A., K. S. Henderson, L. Xi, C.-M. Chow, P. R. Eastwood, and J. A. Dempsey. Neural-mechanical coupling of breathing in REM sleep. J. Appl.Physiol. 83(6): 1923-1932, 1997.During rapid-eye-movement (REM) sleep theventilatory response to airway occlusion is reduced. Possiblemechanisms are reduced chemosensitivity, mechanical impairment of thechest wall secondary to the atonia of REM sleep, or phasic REM eventsthat interrupt or fractionate ongoing diaphragm electromyogram (EMG)activity. To differentiate between these possibilities, we studiedthree chronically instrumented dogs before, during, and after15-20 s of airway occlusion during non-REM (NREM) and phasic REMsleep. We found that 1) for a given inspiratory time the integrated diaphragm EMG(Di) was similar or reduced in REM sleep relativeto NREM sleep; 2) for a givenDi in response to airway occlusion and thehyperpnea following occlusion, the mechanical output (flow or pressure)was similar or reduced during REM sleep relative to NREM sleep;3) for comparable durations ofairway occlusion the Di and integratedinspiratory tracheal pressure tended to be smaller and more variable inREM than in NREM sleep, and 4)significant fractionations (caused visible changes in trachealpressure) of the diaphragm EMG during airway occlusion inREM sleep occurred in ~40% of breathing efforts. Thus reducedand/or erratic mechanical output during and after airwayocclusion in REM sleep in terms of flow rate, tidal volume, and/or pressure generation is attributable largely to reduced neural activity of the diaphragm, which in turn is likely attributable to REM effects, causing reduced chemosensitivity at the level of theperipheral chemoreceptors or, more likely, at the central integrator.Chest wall distortion secondary to the atonia of REM sleep maycontribute to the reduced mechanical output following airway occlusionwhen ventilatory drive is highest.

     

Relationship between renal sympathetic nerve activity and arterial pressure during REM sleep in rats

The relationship between renal sympathetic nerve activity (RSNA) and systemic arterial pressure obtained during rapid eye movement (REM) sleep was compared with that obtained in other sleep and awake states. Electrodes for the measurements of RSNA, electrocardiogram, electromyogram, and electroencephalogram and a catheter for the measurement of systemic arterial pressure were implanted while the animals were under aseptic conditions at least 5 days before the experiment. During the transition from non-REM (NREM) to REM sleep, RSNA and heart rate (HR) decreased immediately by 46 +/- 2% (P < 0.05) and 22 +/- 3 beats/min (P < 0.05), respectively, over 3 s after the onset of REM sleep. Meanwhile, systemic arterial pressure increased gradually after the onset of REM sleep, which was apparently independent of the changes in RSNA. During REM sleep, the relationships between RSNA/HR and systemic arterial pressure were dissociated compared with that obtained during the other behavioral states. These data indicate that the interdependency between systemic arterial pressure and RSNA during REM sleep is likely to be modified compared with other behavioral states.     

Control of motoneuron function and muscle tone during REM sleep, REM sleep behavior disorder and cataplexy/narcolepsy

REM sleep triggers a potent suppression of postural muscle tone - i.e., REM atonia. However, motor control during REM sleep is paradoxical because overall brain activity is maximal, but motor output is minimal. The skeletal motor system remains quiescent during REM sleep because somatic motoneurons are powerfully inactivated. Determining the mechanisms triggering loss of motoneuron function during REM sleep is important because breakdown in REM sleep motor control underlies sleep disorders such as REM sleep behavior disorder (RBD) and cataplexy/narcolepsy. For example, RBD is characterized by dramatic REM motor activation resulting in dream enactment and subsequent patient injury. In contrast, cataplexy a pathognomonic symptom of narcolepsy - is caused by the involuntary onset of REM-like atonia during wakefulness. This review highlights recent work from my laboratory that examines how motoneuron function is lost during normal REM sleep and it also identifies potential biochemical mechanisms underlying abnormal motor control in both RBD and cataplexy. First, I show that both GABAB and GABAA/glycine mediated inhibition of motoneurons is required for generating REM atonia. Next, I show that impaired GABA and glycine neurotransmission triggers the cardinal features of RBD in a transgenic mouse model. Last, I show that loss of an excitatory noradrenergic drive onto motoneurons is, at least in part, responsible for the loss of postural muscle tone during cataplexy in narcoleptic mice. Together, this research indicates that multiple transmitters systems are responsible for regulating postural muscle tone during REM sleep, RBD and cataplexy.     

Evoked activity of the cat hypothalamus and amygdala under food motivation and in emotional stress

Amplitude-latency characteristics of auditory evoked potentials (EPs) recorded in bilateral points of the lateral hypothalamus and amygdala were studied under food motivation, in emotional stress (presentation of dogs) and tentative reactions. In the state of hunger, as compared with safety, the latencies of P1, N2 components of EP in hypothalamus, and P1, N2, N3 in amygdala were decreased and their amplitudes were changed. Changes in the left side of both structures were more pronounced. During presentation of dogs, decreases of latencies of all EP components including N1 occurred in hypothalamus and amygdala, changes in hypothalamic potentials were more pronounced on the right side, whereas in the amygdala--on the left side. During tentative responses to emotional-neutral stimuli, the latency of EP increased. It was concluded that sensory reactivity of hypothalamus and amygdala increased in motivational-emotional states. It was supposed that the side of dominance of structure may be related both to the factors of active or passive behavior during fear and the genesis of emotion (motivational or informational).     

The influence of prior wakefulness on REM sleep

Data from studies of naps and of shifted sleep were used to determine the relationship between two measures of rapid eye movement (REM) sleep (percentage of REM in the first 2 hr of sleep and REM latency) and prior wakefulness. For each sample, we calculated the difference between the observed value and that predicted by a cosine function that estimated the circadian rhythm of REM sleep propensity. The difference values were found to correlate reliably with hours and log hours of prior wakefulness. We conclude that while REM sleep is regulated in part by an endogenous circadian oscillator, it is also influenced by the duration of prior wakefulness.     

Paradoxical REM sleep promoting and permitting neuronal networks

Since its electrophysiological identification in the 1950's, the state of REMS or PS has been shown through multiple lines of evidence to be generated by neurons in the oral pontine tegmentum. The perpetration of this paradoxical state that combines cortical activation with the most profound behavioral sleep occurs through interplay between PS-promoting (On) and PS-permitting (Off) cell groups in the pons. Cholinergic cells in the LDTg and PPTg promote PS by initiating processes of both forebrain activation and peripheral muscle atonia. Bearing alpha1-adrenergic receptors, cholinergic cells, which likely project to the forebrain, are excited by NA and active during both W and PS (W/PS-On), when they promote cortical activation. Bearing alpha2-adrenergic receptors, other cholinergic cells, which likely project to the brainstem, are inhibited by NA and thus active selectively during PS (PS-On), when they promote muscle atonia. Noradrenergic, together with serotonergic, neurons, as PS-Off neurons, thus permit PS in part by lifting their inhibition upon the cholinergic PS-On cells. The noradrenergic/serotonergic neurons are inhibited in turn by local GABAergic PS-promoting neurons that may be excited by ACh. Other similarly modulated GABAergic neurons located through the brainstem reticular formation become active to participate in the inhibition of reticulo-spinal and raphe-spinal neurons as well as in the direct inhibition of motor neurons. In contrast, a select group of GABAergic neurons located in the oral pontine reticular formation and possibly inhibited by ACh turn off during PS. These GABAergic PS-permitting neurons release from inhibition the neighboring large glutamatergic neurons of the oral pontine reticular formation, which are likely concomitantly excited by ACh. In tandem with the cholinergic neurons, these glutamatergic reticular neurons propagate the paradoxical forebrain activation and peripheral inactivation that characterize PS.     

Correlation of unit activity of the right and left amygdala in food motivation and emotional stress

Correlation between activities of neurons in the right and left central nuclei of amygdala of rabbits recorded during quiet wakefulness, after 24-h food deprivation, after satiation and during emotional stress (demonstration of a dog) was studied by plotting crosscorrelation histograms. The histogram peaks shifted from zero were observed in 50-67% cases. In hungry animals, in a greater number of cases (52%), the discharge of a neuron in the left amygdala was the first in a pair, and the discharge of the right neuron was delayed (peaks from 10 to 50 and from 130 to 150 ms). The opposite order of discharges was less frequent (36%). When a rabbit saw a dog, the number of common inputs to neurons increased and the leading role of the right amygdalar neurons grew (57%) due to an increase in inhibitory influences from the right to the left amygdala. In most cases, the interaction between amygdalar neurons occurred at the frequencies of the delta range, predominantly, from 2 to 4 Hz.     

杏仁核参与疼痛情绪过程的研究进展

本文综述了近年来关于杏仁核参与疼痛过程的研究进展。疼痛伴随有强烈的情绪反应,而杏仁核是情绪调控中的一个关键核团。最近,越来越多的证据支持杏仁核参与痛觉的编码和调制过程。杏仁核对来自脊髓和三叉神经核的伤害性信息及皮层和丘脑的多种感觉信息进行整合,产生负性情绪,并对疼痛刺激作出相应的行为反应。同时,杏仁核也通过与导水管周围灰质、延髓头端腹内侧区及其它脑干核团的纤维联系参与镇痛过程。