Stress-induced changes in sleep in rodents: models and mechanisms.

Psychological stressors have a prominent effect on sleep in general, and rapid eye movement (REM) sleep in particular. Disruptions in sleep are a prominent feature, and potentially even the hallmark, of posttraumatic stress disorder (PTSD) (Ross, R.J., Ball, W.A., Sullivan, K., Caroff, S., 1989. Sleep disturbance as the hallmark of posttraumatic stress disorder. American Journal of Psychiatry 146, 697-707). Animal models are critical in understanding both the causes and potential treatments of psychiatric disorders. The current review describes a number of studies that have focused on the impact of stress on sleep in rodent models. The studies are also in Table 1, summarizing the effects of stress in 4-h blocks in both the light and dark phases. Although mild stress procedures have sometimes produced increases in REM sleep, more intense stressors appear to model the human condition by leading to disruptions in sleep, particularly REM sleep. We also discuss work conducted by our group and others looking at conditioning as a factor in the temporal extension of stress-related sleep disruptions. Finally, we attempt to describe the probable neural mechanisms of the sleep disruptions. A complete understanding of the neural correlates of stress-induced sleep alterations may lead to novel treatments for a variety of debilitating sleep disorders.

Long-term effect of cued fear conditioning on REM sleep microarchitecture in rats.

STUDY OBJECTIVES: To study long-term effects of conditioned fear on REM sleep (REMS) parameters in albino rats. DESIGN: We have investigated disturbances in sleep architecture, including muscle twitch density as REMS phasic activity, and freezing behavior in wakefulness, upon reexposure to a conditioned stimulus (CS) on Day 1 and Day 14 postconditioning. SUBJECTS: Male Sprague-Dawley rats prepared for polysomnographic recordings. INTERVENTIONS: After baseline sleep recording, the animals in the experimental group received five pairings of a 5-sec tone, co-terminating with a 1-sec, 1 mAfootshock. The control rats received similar numbers of tones and shocks, but explicitly unpaired. On postconditioning days, after reexposure to tones alone, sleep and freezing behavior were recorded. MEASUREMENTS AND RESULTS: Conditioned fear significantly altered REMS microarchitecture (characterized as sequential-REMS [seq-REMS: < or =3 min episode separation] and single-REMS [sin-REMS: >3 min episode separation]) on Day 14. The total amount and number of seq-REMS episodes decreased, while the total amount and number of sin-REMS episodes increased. Further, the CS induced significant increases in freezing and REMS myoclonic twitch density in the experimental group. Reexposure to the CS produced no alterations in controls. CONCLUSIONS: The results suggest that conditioned fear causes REMS alterations, including difficulty in initiating a REMS episode as indicated by the diminution in the number of seq-REMS episodes. Another finding, the increase in phasic activity, agrees with the inference from clinical investigations that retrieval of fearful memories can be associated with the long-term REMS disturbances characteristic of posttraumatic stress disorder.

Hypoglycemia activates arousal-related neurons and increases wake time in adult rats.

Hypoglycemia resulting from excess of exogenous or endogenous insulin elicits central nervous system activation that contributes to counterregulatory hormone secretion. In adult humans without diabetes, hypoglycemia occurring during sleep usually produces cortical activation with awakening. However, in adult humans with type 1 diabetes, hypoglycemic arousal appears blunted or absent. We hypothesized that insulin injection sufficient to produce hypoglycemia would induce awakening in adult male rats. Polysomnographic studies were carried out to characterize the effect of insulin injection on measures of sleep and waking during a circadian time of increased sleep. Compared to a baseline day, insulin treatment more than doubled the time spent awake, from 18.4+/-2.6% after saline injection to 48.0+/-5.5% after insulin. Insulin injection also reduced rapid eye movement sleep (REMS) from 27.3+/-1.8% to 5.6+/-1.3%. The percent of time in non-REM sleep (NREMS) sleep was not different between saline and insulin days, however, NREMS after insulin was fragmented, with increased number and decreased duration of episodes. These electrophysiological data indicate that insulin-induced hypoglycemia is an arousing stimulus in rats, as in nondiabetic adult humans. We also studied the effect of insulin on activation of selected arousal-related neurons using immunohistochemical detection of Fos. Fos-immunoreactivity increased in orexin (OX) neurons after insulin, from 8.7+/-4.9% after saline injection to 37+/-9% after insulin. Basal forebrain cholinergic nuclei also showed increased Fos-immunoreactivity after insulin. These correlated behavioral and histological data provide targets for future studies of the neural pathways underlying hypoglycemic arousal.

Modulation of the ultradian human nasal cycle by sleep stage and body position.

OBJECTIVE:: The nasal cycle, which is present in a significant number of people, is an ultradian side-to-side rhythm of nasal engorgement associated with cyclic autonomic activity. We studied the nasal cycle during REM/non-REM sleep stages and examined the potentially confounding influence of body position on lateralized nasal airflow. METHODS:: Left- and right-side nasal airflow was measured in six subjects during an eight-hour sleep period using nasal thermistors. Polysomnography was performed. Simultaneously, body positions were monitored using a video camera in conjunction with infrared lighting. RESULTS:: Significantly greater airflow occurred through the right nasal chamber (relative to the left) during periods of REM sleep than during periods of non-REM sleep (p<0.001). Both body position (p < 0.001) and sleep stage (p < 0.001) influenced nasal airflow lateralization. CONCLUSIONS:: This study demonstrates that the lateralization of nasal airflow and sleep stage are related. Some types of asymmetrical somatosensory stimulation can alter this relationship.

Social partnering alters sleep in fear-conditioned Wistar rats.

Social support, when provided following a traumatic experience, is associated with a lower incidence of stress-related psychiatric disorders. Our hypothesis was that providing a social interaction period with a naive conspecific would improve sleep architecture in response to cued fear conditioning in Wistar rats. Rats were randomly assigned to either the socially isolated or socially partnered groups. Rats assigned to the socially isolated group were individually housed following electrode implantation and fear conditioning. Rats assigned to the socially partnered group were initially paired-housed, and then one rat from each pair was randomly chosen for sleep electrode implantation and fear conditioning. Rats from both groups were habituated to a recording chamber, and baseline sleep was recorded over 22 hours. One day later (Training Day), they were fear-conditioned to 10 presentations of a tone (800 Hz, 90 dB, 5 sec) co-terminating with a mild electric foot shock (1.0 mA, 0.5 sec), at 30-sec intervals. While rats in the socially isolated group were left undisturbed in their home cage for 30-min, socially partnered rats interacted for 30 minutes with their non-stressed rat partner immediately after fear conditioning and while the auditory tones were presented on Days 1 and 14. The results indicated that social interaction increased sleep efficiency in partnered rats compared to isolated rats following the fear conditioning procedure. This was due to an increase in the amount of rapid eye movement sleep (REMS) during the light phase. Evaluation of REMS microarchitecture revealed that the increase in REMS was due to an increase in the number of single REMS episodes (siREMS), which represented a more consolidated REMS pattern. A surprising finding was that partnered rats had a greater number of sequential REMS episodes (seqREMS) at Baseline, on the Training Day and on Day 1 when compared to isolated rats. The greater number of seqREMS episodes in partnered rats may be due to the partnering procedure and not fear conditioning, as the effect was also seen at Baseline. Thus it appears that while the partnering procedure may have given rise to a fragmented REMS pattern, social partnering promoted a greater consolidation of REMS in response to the fear conditioning procedure.

Corticotropin-releasing factor microinjection into the central nucleus of the amygdala alters REM sleep.

Psychological stressors have a prominent effect on rapid eye movement sleep (REMS) in humans and animals. We hypothesized that the stress-related neurochemical corticotropin-releasing factor (CRF), acting in the amygdala, could initiate neural events that lead to REMS alterations. Therefore, we made bilateral microinjections of three different doses of CRF into the central nucleus of the amygdala (CeA) in five rats. Only the lowest dose of CRF (1 ng) induced a change in sleep, specifically REMS, during the 4-h post-injection period. Thus, REMS alterations following psychological stress may depend, in part, on CRF release in the CeA.

A rodent model of sleep disturbances in posttraumatic stress disorder: the role of context after fear conditioning.

BACKGROUND: A prominent sleep disturbance, likely including a disruption of rapid eye movement sleep (REMS) continuity, characterizes posttraumatic stress disorder (PTSD). We set out to develop a fear conditioning paradigm in rats that displays alterations in sleep architecture analogous to those in PTSD. METHODS: Baseline polysomnographic recordings of rats were performed in a neutral context to which the rats had been habituated for several days. Rats were then shock- or mock-trained in a distinctly different context, and their sleep was studied the following day in that context. A separate group of rats was shock-trained and studied in the neutral context on the following 2 days. RESULTS: Rats that slept in the neutral context exhibited a REMS-selective increase in sleep 24 hours after training and increases in REMS and non-REMS 48 hours after training. In contrast, rats that slept in the presence of situational reminders of the training context exhibited a REMS-selective decrease in sleep 24 hours later. Animals that were mock-trained showed no changes in sleep. CONCLUSIONS: Shock training induced days-long changes in sleep architecture that were disrupted when the animal was exposed to situational reminders of the training context.

Tetrodotoxin inactivation of pontine regions: influence on sleep-wake states.

Studies using various methodologies have implicated n. reticularis pontis oralis (RPO) and n. subcoeruleus (SubC) in the generation of rapid eye movement sleep (REM). In rats, electrolytic lesions in these regions may give rise to the phenomenon of REM without atonia (REM-A), in which the electrophysiological features of REM are normal except that atonia is absent and elaborate behaviors may be exhibited. However, electrolytic lesions damage both cell bodies and fibers of passage, and the neural reorganization and adaptation that can occur post-lesion can complicate interpretation. Tetrodotoxin (TTX) is a sodium channel blocker that temporarily inactivates both neurons and fibers of passage and thus may be functionally equivalent to an electrolytic lesion, but without allowing time for neural adaptation. In this study, we examined the influence of microinjections of TTX into RPO and SubC on sleep in freely behaving rats. Rats (90 day old male Sprague-Dawley) were implanted with electrodes for recording EEG and EMG. Guide cannulae were implanted aimed into RPO or SubC. Each animal received one unilateral microinjection (TTXUH: 5.0 ng/0.2 microl) and two bilateral microinjections (TTXBL: 2.5 ng/0.1 microl; TTXBH: 5.0 ng/0.2 microl) of TTX, and control microinjections of saline alone (SAL). The injections were made 2 h following lights on, and sleep was recorded for the subsequent 22 h. Sleep was scored from computerized records in 10 s epochs. Recordings from the 10-h light period and the 12-h dark period were examined separately. TTX inactivation of RPO could decrease REM and non-REM (NREM), whereas inactivation of SubC produced relatively more specific decreases in REM with smaller effects on NREM. The results complement studies that have implicated RPO and SubC in REM generation. REM-A was not observed, suggesting that REM-A is a complex phenomenon that requires time for reorganization of the nervous system after insult.

Sleep-related neurons in the central nucleus of the amygdala of rats and their modulation by the dorsal raphe nucleus.

The amygdala (AMY) plays an important role in initiating appropriate neurobehavioral responses to emotionally arousing events. Its major efferents from the central nucleus (Ace) to the basal forebrain, hypothalamus and brainstem permit it to influence sleep mechanisms. To characterize further the neuronal activity of AMY during sleep and wakefulness, we recorded single neuronal activity in Ace across behavioral states in freely moving, normally behaving rats. Of the 49 neurons recorded from Ace, 24 neurons had firing patterns related to sleep-wakefulness (S-W). Of these, 50% (n = 12) had a high firing frequency during wakefulness (W) or both W and REM sleep (REM), 12% (n = 3) were non-REM (NREM)-related, 17% (n = 4) had a high firing rate in REM (REM-ON), and 20% (n = 5) fired at a low rate during REM. Because serotonin introduced into AMY during REM induces short-latency changes of state, we also studied the effects of low frequency (1 Hz) electrical stimulation of the dorsal raphe nucleus (DRN) on Ace neurons. All REM-ON neurons recorded from Ace were inhibited by DRN stimulation, and other cell types were unaffected. Thus, we found that the majority of cells in Ace related to S-W fired slowly during NREM and increased their discharge during W and/or REM, and that the DRN has the potential for modulating the spontaneous activity of REM-ON cells in rats.

Differential effect of sleep-wake states on lingual and dorsal neck muscle activity in rats.

Postural tone is reduced during slow-wave sleep (SWS) and absent during rapid eye movement sleep (REMS). In obstructive sleep apnea subjects, upper airway dilating muscles, including those of the tongue, show a similar pattern; this contributes to sleep-related airway obstructions. However, in healthy subjects, state-dependent changes in the activity of pharyngeal muscles are variable. In seven chronically instrumented Sprague-Dawley rats, an animal model used to study sleep and sleep-disordered breathing, we quantified lingual and postural muscle activity across the sleep-wake states by measuring the root mean square levels of the electromyograms (EMG) in successive 10s intervals collected during 2h of recording at a constant circadian time (1-3p.m.). The nuchal EMG was low and steady during SWS and further reduced with occasional twitches during REMS. In contrast, the mean lingual EMG during SWS was only 5.9+/-1.6% (S.E.) of its mean in wakefulness, and during REMS, it increased to 46+/-15% (S.E.) (p<0.03) due to the appearance of phasic bursts, the intensity of which progressively increased. The lingual and nuchal activities also had different time courses during state transitions. In obstructive sleep apnea subjects, the sleep-wake changes in the activity of pharyngeal muscles may become similar to those in postural muscles as a result of pharyngeal tone adaptations to the disorder.

A serotonergic (5-HT2) receptor mechanism in the laterodorsal tegmental nucleus participates in regulating the pattern of rapid-eye-movement sleep occurrence in the rat.

Serotonin [5-hydroxytryptamine (5-HT)] plays an inhibitory role in rapid-eye-movement (REM) sleep although the exact mechanism(s) and site(s) of action are not known. It is commonly assumed that 5-HT exerts its influence on REM sleep via input from the dorsal raphe nucleus (DRN) directly onto cholinergic neurons involved in the generation of REM sleep. 5-HT(2) receptor sites have been found on cholinergic neurons in the laterodorsal tegmental nucleus (LDT) and pedunculopontine tegmental nucleus (PPT). We locally microinjected the 5-HT(2) agonist DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl) and the 5-HT(2) antagonist, ketanserin, in LDT in rats to determine whether these receptor sites are involved in the regulation of behavioral states. DOI and ketanserin primarily affected REM sleep, by significantly decreasing or increasing, respectively, the number, but not the duration, of REM sleep episodes. DOI specifically decreased the occurrence of clusters of REM sleep episodes appearing at intervals less than or equal to 3 min (sequential episodes) without affecting single episodes separated by more than 3 min. An opposite effect of ketanserin on REM sleep clusters, although not statistically significant, was observed.

The central nucleus of the amygdala and the wake-promoting effects of modafinil.

Modafinil, a novel non-amphetamine stimulant recently approved for the treatment of narcolepsy, has been shown to increase waking in both animals and humans. However, its mechanism of action is currently unknown. Earlier research into the brain structures responsible for the wake-producing actions of modafinil implicated the central nucleus of the amygdala (ACe) as a possible site of action [Neuroscience 87 (1998) 905-911; Neurosci. Lett. 241 (1998) 95-98]. The present experiments were designed to test the hypothesis that the ACe is, at least in part, involved in the wake-producing actions of modafinil. In the first experiment, rats with lesions of the ACe were injected systemically with varying doses of modafinil and sleep was recorded. At the highest dose, modafinil significantly increased waking and decreased sleep. However, there was no interaction between the lesion and the effect of the drug. In the second experiment, varying doses of modafinil were injected directly into the ACe and sleep was recorded. Injection of modafinil into the ACe did not affect sleep architecture. Thus, ACe does not play a simple role in modafinil's wake-promoting action. We suggest that more complex testing will be required to elucidate its role.

Diagnosis of rapid eye movement sleep disorder with electroencephalography and treatment with tricyclic antidepressants in a dog.

A 9-month-old, female Labrador retriever mix was presented for two types of seizure-like episodes, one of which occurred only during sleep. The two types of episodes were morphologically distinct. An electroencephalogram (EEG) demonstrated that the sleep-associated episodes occurred during rapid eye movement (REM) sleep, supporting a diagnosis of a REM behavior disorder. Based on their morphology and response to antiseizure medications, the waking episodes were diagnosed as seizures. The animal was also diagnosed with an obsessive-compulsive and generalized anxiety disorder. The REM behavior disorder and anxiety-related behaviors improved with tricyclic antidepressant therapy.

Time- and behavioral state-dependent changes in posterior hypothalamic GABAA receptors contribute to the regulation of sleep.

Sleep-wake behavior is regulated by a circadian rhythm, homeostatically and by additional mechanisms that determine the timing of slow-wave sleep and rapid eye movement sleep (REMS) episodes. The posterior hypothalamus coordinates the neural and humoral signals with the rest-activity cycle. It contains wake-active neurons, and is a site where stimulation of inhibitory GABAA receptors promotes sleep, whereas their antagonism enhances wakefulness. We explored whether GABAergic mechanisms present in the posterior hypothalamus contribute to the homeostatic and other aspects of sleep-wake regulation. Using micropunches of tissue extracted from either the perifornical (PF) or dorsomedial (DM) regions of the posterior hypothalamus of rats, we determined that mRNA levels for selected subunits of GABAA receptors (ß1, ß3 and ε) were higher at the end of the active period or following sleep deprivation, when the need for sleep is high, than after several hours of sleep, when sleep need is partially fulfilled. Such a pattern was present in the PF region only, and was consistent with changes in ß1 subunit and GABA synthesizing enzyme (GAD) protein levels. In contrast, in the DM region, the levels of GABAA receptor subunit mRNAs and proteins (α1, α2, ß1) and GAD varied with circadian time, but were not responsive to sleep deprivation. Separate experiments with sleep-wake monitoring and local perfusion of the PF region with the GABAA receptor antagonist bicuculline revealed that the antagonist had a weaker sleep-reducing effect when sleep need was enhanced by sleep deprivation and that the increased amount of REMS characteristic of the late sleep period was dependent on endogenous GABAergic inhibition. These results support the concept that a varying magnitude of GABAergic inhibition exerted within the PF region contributes to the homeostatic regulation of sleep and shapes its temporal pattern, whereas GABAergic mechanisms in the DM region contribute to circadian regulation.

The α1 adrenoceptor antagonist prazosin enhances sleep continuity in fear-conditioned Wistar-Kyoto rats.

Fragmentation of rapid eye movement sleep (REMS) is well described in individuals with posttraumatic stress disorder (PTSD) and likely has significant functional consequences. Fear-conditioned rodents may offer an attractive model of the changes in sleep that characterize PTSD. Following fear conditioning (FC), Wistar-Kyoto (WKY) rats, a strain known to be particularly stress-sensitive, have increased REMS fragmentation that can be quantified as a shift in the distribution of REMS episodes towards the more frequent occurrence of sequential REMS (inter-REMS episode interval≤3 min) vs. single REMS (interval>3 min). The α1 adrenoceptor antagonist prazosin has demonstrated efficacy in normalizing sleep in PTSD. To determine the utility of fear-conditioned WKY rats as a model of sleep disturbances typical of PTSD and as a platform for the development of new treatments, we tested the hypothesis that prazosin would reduce REMS fragmentation in fear-conditioned WKY rats. Sleep parameters and freezing (a standard measure of anxiety in rodents) were quantified at baseline and on Days 1, 7, and 14 following FC, with either prazosin (0.01mg/kg, i.p.) or vehicle injections administered prior to testing in a between-group design. Fear conditioning was achieved by pairing tones with a mild electric foot shock (1.0mA, 0.5s). One, 7, and 14 days following FC, prazosin or vehicle was injected, the tone was presented, freezing was measured, and then sleep was recorded from 11 AM to 3 PM. WKY rats given prazosin, compared to those given vehicle, had a lower amount of seq-REMS relative to total REMS time 14 days after FC. They also had a shorter non-REMS latency and fewer non-REMS arousals at baseline and on Days 1 and 7 after FC. Thus, in FC rats, prazosin reduced both REMS fragmentation and non-REMS discontinuity.

Coming to grips with a "new" state of consciousness: the study of rapid-eye-movement sleep in the 1960s.

The recognition of rapid-eye-movement sleep (REM) and its association with dreaming in 1953 by Aserinsky and Kleitman opened a new world to explore in the brain. Discussions at two major symposia in the early 1960s reveal that a state with characteristics resembling both wakefulness and sleep was overturning accepted views of the regulation of the two states. Participants grappled with the idea that cortical activation could occur during sleep. They struggled with picking a name that would capture the essence of REM without focusing on just one aspect of the state. Questioning whether REM in cats could be homologous with that of humans suggested an anthropocentric focus on human dreaming as the essence of the state. The need for biochemical studies was evident given that deprivation of REM caused a rebound in the amount of subsequent REM, which indicated that simple synaptic activity could not support this phenomenon.

Modulation of the ultradian human nasal cycle by sleep stage and body position / Modulação do ciclo nasal humano ultradiano pelo estágio do sono e a posição corporal

ABSTRACT Objective: The nasal cycle, which is present in a significant number of people, is an ultradian side-to-side rhythm of nasal engorgement associated with cyclic autonomic activity. We studied the nasal cycle during REM/non-REM sleep stages and examined the potentially confounding influence of body position on lateralized nasal airflow. Methods: Left- and right-side nasal airflow was measured in six subjects during an eight-hour sleep period using nasal thermistors. Polysomnography was performed. Simultaneously, body positions were monitored using a video camera in conjunction with infrared lighting. Results: Significantly greater airflow occurred through the right nasal chamber (relative to the left) during periods of REM sleep than during periods of non-REM sleep (p<0.001). Both body position (p < 0.001) and sleep stage (p < 0.001) influenced nasal airflow lateralization. Conclusions: This study demonstrates that the lateralization of nasal airflow and sleep stage are related. Some types of asymmetrical somatosensory stimulation can alter this relationship.

RESUMO Objetivo: O ciclo nasal é um ritmo ultradiano de lado a lado de ingurgitamento associado com o ciclo da atividade autônoma. O objetivo deste estudo foi abordar a questão assim como a relação presente entre o ciclo nasal e os estágios de sono REM/não-REM. Também analisamos a confusão potencial da influência da posição corporal no fluxo de ar nasal. Métodos: Mensuramos o ciclo nasal em seis sujeitos durante um sono de oito horas usando um termistor nasal. Foi realizada uma polissonografia. Simultaneamente, nós monitoramos a posição corporal usando uma câmera de vídeo juntamente com luzes infravermelhas. Resultados: Um fluxo de ar maior ocorreu através da cavidade nasal direita durante as fases de sono REM do que nos períodos de sono não-REM (p < 0,001). Assim como a posição corporal [F(2.2340) = 86,99, p < 0,001] e o estágio de sono [F(1.2340) = 234.82, p < 0,001] influenciaram a lateralização do fluxo de ar nasal. Conclusões: Este estudo evidencia que a lateralização do fluxo de ar nasal e o estágio do sono estão relacionados. Alguns tipos de estimulação somatosensitiva assimétrica podem alterar esta relação.

Fear conditioning fragments REM sleep in stress-sensitive Wistar-Kyoto, but not Wistar, rats.

Pavlovian conditioning is commonly used to investigate the mechanisms of fear learning. Because the Wistar-Kyoto (WKY) rat strain is particularly stress-sensitive, we investigated the effects of a psychological stressor on sleep in WKY compared to Wistar (WIS) rats. Male WKY and WIS rats were either fear-conditioned to tone cues or received electric foot shocks alone. In the fear-conditioning procedure, animals were exposed to 10 tones (800 Hz, 90 dB, 5s), each co-terminating with a foot shock (1.0 mA, 0.5s), at 30-s intervals. In the shock stress procedure, animals received 10 foot shocks at 30-s intervals, without tones. All subjects underwent a tone-only test both 24h (Day 1) and again two weeks (Day 14) later. Rapid eye movement sleep (REMS) continuity was investigated by partitioning REMS episodes into single (inter-REMS episode interval >3 min) and sequential (interval ≤ 3 min) episodes. In the fear-conditioned group, freezing increased from baseline in both strains, but the increase was maintained on Day 14 in WKY rats only. In fear-conditioned WKY rats, total REMS amount increased on Day 1, sequential REMS amount increased on Day 1 and Day 14, and single REMS amount decreased on Day 14. Alterations were due to changes in the number of sequential and single REMS episodes. Shock stress had no significant effect on REMS microarchitecture in either strain. The shift toward sequential REMS in fear-conditioned WKY rats may represent REMS fragmentation, and may provide a model for investigating the neurobiological mechanisms of sleep disturbances reported in posttraumatic stress disorder.

Reduced γ range activity at REM sleep onset and termination in fear-conditioned Wistar-Kyoto rats.

Recent investigations of rapid eye movement sleep (REMS) continuity have emphasized the importance of transitions both into and out of REMS. We have previously reported that, compared to Wistar rats (WIS), Wistar-Kyoto rats (WKY) responded to fear conditioning (FC) with more fragmented REMS. Gamma oscillations in the electroencephalogram (EEG) are synchronized throughout the brain in periods of focused attention, and such synchronization of cell assemblies in the brain may represent a temporal binding mechanism. Therefore, we examined the effects of FC on EEG gamma range activity (30-50Hz) at REMS transitions in WKY compared to WIS. Relative power in the gamma range (measured as a percent of total power) at Baseline and upon re-exposure to the fear-inducing conditioning stimulus was measured 35s before REMS onset to 105s after REMS onset (ARO) and 85s before REMS termination (BRT) to 35s after REMS termination. After baseline recording, rats received 10 tones, each co-terminating with an electric foot shock. On Days 1 and 14 post-conditioning, rats were re-exposed to three tones. Fast-Fourier transforms created power spectral data in the gamma frequency domain. Relative power was extracted from an average of 4-5 REMS transitions. Relative gamma power was always higher in WIS. On Day 14, at 15s and 25s ARO, WKY had significant increases in relative gamma power from Baseline. WIS had a significant increase on Day 1 at 25s ARO. Despite the increases in relative gamma power, WKY never achieved levels attained by WIS. Moreover, at 5s BRT, only WKY had a significant decrease in relative gamma power from Baseline to Day 14. Gamma range activity may indicate neural activity underlying maintenance of REMS continuity. Low relative gamma power at REMS transitions may be associated with increased REMS fragmentation in WKY after FC.