Time structure analysis of leg movements during sleep in REM sleep behavior disorder

STUDY OBJECTIVES: To compare the time structure of leg movements (LM) during sleep of patients with rapid eye movement (REM) sleep behavior disorder (RBD) with that of patients with restless legs syndrome (RLS) or control subjects. DESIGN: The polysomnographically recorded tibialis anterior activity during sleep was analyzed by means of a new approach able to consider duration, intermovement interval, sleep stage and time of night distribution, and periodicity. PATIENTS AND PARTICIPANTS: Twenty patients with idiopathic RBD, 37 with idiopathic RLS and 14 age-matched control subjects were consecutively recruited. MEASUREMENTS AND RESULTS: Most patients with RBD (85%) presented periodic leg movements during sleep (PLMS). PLMS occurred more frequently during non-REM sleep in patients with RLS and during REM sleep in patients with RBD. PLMS were shorter in duration, less often bilateral, and with a higher intermovement interval in patients with RBD compared to those with RLS. The number of PLMS decreased across the night in patients with RBD and in those with RLS, but not in control subjects. In all subjects, LM periodicity clearly depended on sleep state, with higher values during non-REM than during REM sleep. Patients with RBD showed a lower LM periodicity, compared with patients with RLS, in each of the sleep states. CONCLUSIONS: Significant differences, together with some similarities in LM time structure, were observed between patients with RBD and those with RLS; for this reason, our approach seems to indicate that their phenotype might be dependent on 2 factors: disease and sleep stage.     

Quantification of electromyographic activity during REM sleep in multiple muscles in REM sleep behavior disorder

STUDY OBJECTIVES: The aim of our study was to determine which muscle or combination of muscles (either axial or limb muscles, lower or upper limb muscles, or proximal or distal limb muscles) provides the highest rates of rapid eye movement (REM) sleep phasic electromyographic (EMG) activity seen in patients with REM sleep behavior disorder (RBD). SETTING: Two university hospital sleep disorders centers. PARTICIPANTS: Seventeen patients with idiopathic RBD (n = 8) and RBD secondary to Parkinson disease (n = 9). INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: Patients underwent polysomnography, including EMG recording of 13 different muscles. Phasic EMG activity in REM sleep was quantified for each muscle separately. A mean of 1459.6 +/- 613.8 three-second REM sleep mini-epochs were scored per patient. Mean percentages of phasic EMG activity were mentalis (42 +/- 19), flexor digitorum superficialis (29 +/- 13), extensor digitorum brevis (23 +/- 12), abductor pollicis brevis (22 +/- 11), sternocleidomastoid (22 +/- 12), deltoid (19 +/- 11), biceps brachii (19 +/- 11), gastrocnemius (18 +/- 9), tibialis anterior (right, 17 +/- 12; left, 16 +/- 10), rectus femoris (left, 11 +/- 6; right, 9 +/- 6), and thoraco-lumbar paraspinal muscles (6 +/- 5). The mentalis muscle provided significantly higher rates of excessive phasic EMG activity than all other muscles but only detected 55% of all the mini-epochs with phasic EMG activity. Simultaneous recording of the mentalis, flexor digitorum superficialis, and extensor digitorum brevis muscles detected 82% of all mini-epochs containing phasic EMG activity. This combination provided higher rates of EMG activity than any other 3-muscle combination. Excessive phasic EMG activity was more frequent in distal than in proximal muscles, both in upper and lower limbs. CONCLUSION: Simultaneous recording of the mentalis, flexor digitorum superficialis, and extensor digitorum brevis muscles provided the highest rates of REM sleep phasic EMG activity in subjects with RBD.     

Increased muscle activity during sleep and more RBD symptoms in H1N1-(Pandemrix)-vaccinated narcolepsy type 1 patients compared with their non-narcoleptic siblings

Study ObjectivesNarcolepsy type 1 (NT1) is characterized by unstable sleep-wake and muscle tonus regulation during sleep. We characterized dream enactment and muscle activity during sleep in a cohort of post-H1N1 NT1 patients and their siblings, and analyzed whether clinical phenotypic characteristics and major risk factors are associated with increased muscle activity.MethodsRBD symptoms and polysomnography m. tibialis anterior electromyographical signals [long (0.5–15 s); short (0.1–0.49 s)] were compared between 114 post-H1N1 NT1 patients and 89 non-narcoleptic siblings. Association sub-analyses with RBD symptoms, narcoleptic symptoms, CSF hypocretin-1 levels, and major risk factors [H1N1-(Pandemrix)-vaccination, HLA-DQB1*06:02-positivity] were performed.ResultsRBD symptoms, REM and NREM long muscle activity indices and REM short muscle activity index were significantly higher in NT1 patients than siblings (all p < 0.001). Patients with undetectable CSF hypocretin-1 levels (<40 pg/ml) had significantly more NREM periodic long muscle activity than patients with low but detectable levels (40–150 pg/ml) (p = 0.047). In siblings, REM and NREM sleep muscle activity indices were not associated with RBD symptoms, other narcolepsy symptoms, or HLA-DQB1*06:02-positivity. H1N1-(Pandemrix)-vaccination status did not predict muscle activity indices in patients or siblings.ConclusionIncreased REM and NREM muscle activity and more RBD symptoms is characteristic of NT1, and muscle activity severity is predicted by hypocretin deficiency severity but not by H1N1-(Pandemrix)-vaccination status. In the patients’ non-narcoleptic siblings, neither RBD symptoms, core narcoleptic symptoms, nor the major NT1 risk factors is associated with muscle activity during sleep, hence not indicative of a phenotypic continuum.     

A quantitative statistical analysis of the submentalis muscle EMG amplitude during sleep in normal controls and patients with REM sleep behavior disorder

The aim of this study was to evaluate quantitatively the amplitude of the submentalis muscle EMG activity during sleep in controls and in patients with idiopathic REM sleep behavior disorder (RBD) or with RBD and multiple system atrophy (MSA). We recruited 21 patients with idiopathic RBD, 10 with MSA, 10 age-matched and 24 young normal controls. The average amplitude of the rectified submentalis muscle EMG signal was used for the assessment of atonia and a Sleep Atonia Index was developed; moreover, also chin muscle activations were detected and their duration and interval analyzed. The Sleep Atonia Index was able to distinguish clearly REM from NREM sleep in normal controls with values very close to 1 in young normal subjects and only slightly (but significantly) lower in old controls. Idiopathic RBD patients showed a further significant decrease of this index; MSA patients showed the lowest values of REM Sleep Atonia Index, which were very well distinguishable from those of normal controls and of idiopathic RBD patients. The distribution of the duration of chin activations was monomodal in all groups, with idiopathic RBD patients showing the highest levels. This study is a really quantitative attempt to provide practical indices for the objective evaluation of EMG atonia during REM sleep and of EMG activations. Our proposed Sleep Atonia Index can have a practical application in the clinical evaluations of patients and represents an additional useful parameters to be used in conjunction with the other criteria for the diagnosis of this sleep motor disorder.     

Searching for a marker of REM sleep behavior disorder: submentalis muscle EMG amplitude analysis during sleep in patients with narcolepsy/cataplexy

STUDY OBJECTIVES: To evaluate the amplitude of submentalis muscle EMG activity during sleep in patients with narcolepsy/cataplexy with or without REM sleep behavior disorder (RBD). DESIGN: Observational study with consecutive recruitment. SETTINGS: Sleep laboratory. PATIENTS: Thirty-four patients with narcolepsy/cataplexy and 35 age-matched normal controls. MEASUREMENTS AND RESULTS: Half the patients (17 subjects) had a clinical and video polysomnographic diagnosis of RBD. The average amplitude of the rectified submentalis muscle EMG signal was used to assess muscle atonia, and the new REM sleep Atonia Index was computed. Chin muscle activations were detected and their duration and interval analyzed. REM sleep Atonia Index was lower in both patient groups (with narcolepsy patients with RBD showing the lowest values) with respect to controls, and it did not correlate with age as it did in controls. The total number of chin EMG activations was significantly higher in both patient groups than controls. No significant differences were found between the two groups of patients, although more chin EMG activations were noted in narcolepsy patients with RBD than those without. CONCLUSIONS: Elevated muscle activity during REM sleep is the only polysomnographic marker of RBD. This study shows that polysomnographically evident RBD is present in many patients with narcolepsy/ cataplexy. This condition might be specific to narcolepsy/cataplexy, reflecting a peculiar form of REM sleep related motor dyscontrol (i.e., status dissociatus), paving the way to enacting dream behaviors, and correlated with the specific neurochemical and neuropathological substrate of narcolepsy/cataplexy.     

Scoring of large muscle group movements during sleep: an International Restless Legs Syndrome Study Group position statement

There is a gap in the manuals for scoring sleep-related movements because of the absence of rules for scoring large movements. A taskforce of the International Restless Legs Syndrome Study Group (IRLSSG) elaborated rules that define the detection and quantification of movements involving large muscle groups. Consensus on each of the criteria in this article was reached by testing the presence of consensus on a first proposal; if no consensus was achieved, the concerns were considered and used to modify the proposal. This process was iterated until consensus was reached. A preliminary analysis of the duration of movements involving large muscle groups was also carried out on data from two previous studies, which, however, used a visual analysis of video-polysomnographic (PSG) recordings obtained from children or adults. Technical specifications and scoring rules were designed for the detection and quantification of large muscle group movements during sleep with a duration between 3 and 45 seconds in adults or 3 and 30 seconds in children, characterized by an increase in electromyographic activity and/or the occurrence of movement artifact in any combination of at least two recommended channels and not meeting the criteria for any other type of movement. Large muscle group movements are often accompanied by sleep stage changes, arousals, awakenings, and heart rate rises. The absence of clear and detailed rules defining them has likely impeded the development of studies that might disclose their clinical relevance; these new rules fill this gap.     

Sequence analysis of leg movements during sleep with different intervals (<10, 10–90 and >90 s) in restless legs syndrome

The aim of this study was to define the time structure of leg movements during sleep occurring with an intermovement interval (onset‐to‐onset) shorter than 10 s in patients with restless legs syndrome and controls, and to compare it to the structure of movements with intervals of 10–90 s or >90 s. Polysomnographic recordings of 141 untreated patients and 68 age‐matched normal controls were analysed. All movements were detected and classified into three categories, separated by intervals of <10, 10–90 or >90 s. The number of movements included in each category was significantly higher in patients than in controls. The movements with an interval of >90 s occurred steadily during the night, whereas the hourly distribution of movements with intervals of <10 or 10–90 s was decreasing or bell‐shaped in patients or controls, respectively. Movements with an interval of <10 s tended to have a shorter duration and constituted shorter sequences than movements with intervals of 10–90 or >90 s. The time structure features of the three categories of movements considered in this study were found to be clearly different. This, together with previous observations on the differential effects of dopamine agonists on movements with different intervals, suggests that movements with intervals of <10 and >90 s are regulated by neurotransmitter mechanisms different from those modulating movements with an interval of 10–90 s.     

The role of the substantia nigra in a striatally-evoked motor response in the rat: effects of intranigral drugs and lesions

Turning of the head towards the contralateral side was induced in the conscious unrestrained rat by electrical stimulation of the neostriatum through permanent indwelling electrodes. The importance of the substantia nigra in mediating this response was investigated using electrolytic and kainic acid lesions. Contralateral head-turning was attenuated by small electrolytic lesions of the substantia nigra on the stimulated side and abolished by large electrolytic lesions that destroyed the entire nucleus. The injection of kainic acid into the substantia nigra caused persistent circling behaviour but did not modify the head-turn response to striatal stimulation; these injections destroyed some of the neurons in the pars compacta but the majority of neurons in the pars reticulata were undamaged. Drugs that alter the function of nigral neurotransmitters were injected through an indwelling cannula in the zona reticulata. Interference with the function of γ-aminobutyrate in the nigra produced small changes in the latency of the motor response. However the following drugs did not modify the response: substance P, nicotine, atropine, apomorphine, glutamic acid diethylester, glycine, strychnine, met-enkephalin and 5-methoxy-N,N-dimethyltryptamine.It is concluded that descending projections from the basal ganglia which pass through or very close to the nigra, probably without forming synapses in the pars reticulata, may be important for the mediation of the striatally-evoked response.     

Cognitive dysfunction and REM sleep behavior disorder: Key findings in the literature and preliminary longitudinal findings

A considerable proportion of subjects initially diagnosed with idiopathic REM sleep behavior disorder (iRBD) are reported to convert to a neurodegenerative disorder, mainly synucleinopathies.     

帕金森病睡眠障碍患者的血浆orexin A浓度变化及其影响因素分析

目的:探讨帕金森病(PD)睡眠障碍患者的血浆orexin A浓度变化,分析其可能影响因素.方法:采用UPDRS-Ⅲ评分、用药调查表、多项睡眠图(PSG)监测及次日多次睡眠潜伏期试验分别对25例PD患者的疾病严重程度、多巴胺能药物应用、睡眠结构、平均睡眠潜伏期等情况进行评定和计算;使用放射免疫分析法对25例临床确诊的PD患者和20例无明显中枢神经系统(CNS)疾病的对照组进行血浆orexin A浓度测定;分析PD患者血浆orexin A浓度与其睡眠结构、平均睡眠潜伏期、服用多巴胺能药物剂量间的相关性.结果:PD组中25例患者的血浆orexin A浓度[(7.72±3.44) pg/ml]和20例对照组的血浆orexin A浓度[(6.04±3.22) pg/ml]比较差异无统计学意义(t=1.669,P＞0.05);PD伴眼快动睡眠期精神行为障碍(RBD)组12例的血浆orexin A浓度[(6.93±2.67)pg/ml]和PD不伴RBD组的13例血浆orexin A浓度[(8.45±3.99)pg/ml]比较差异无统计学意义(t=-1.108,P＞0.05);PD伴SAHS组12例的血浆orexin A浓度[(7.40±3.56)pg/ml]和PD不伴SAHS组13例的血浆orexin A浓度[(8.01±3.44)pg/ml]比较差异无统计学意义(t=-0.433,P＞0.05);多元逐步线性回归分析显示PD患者的血浆orexin A浓度与平均睡眠潜伏期(β=-0.382,95％ CI:-0.708～-0.056)、左旋多巴日等效剂量(β=-0.011,95％ CI:-0.018～-0.004)呈负相关(t=-2.433、-3.132,P＜0.05).结论:PD患者血浆orexin A浓度变化受多巴胺能药物剂量及日间平均睡眠潜伏期的影响.     

A complementary relationship between wake and REM sleep in the auditory system: a pre-sleep increase of middle-ear muscle activity (MEMA) causes a decrease of MEMA during sleep

Since some evidence has supported a complementary relationship between waking and REM-sleep eye movement (variations in frequency, amplitude, or direction of waking saccades have been found to inversely affect the corresponding parameters of rapid eye movements), the present study assessed whether this relationship can also be shown for other phasic components of REM sleep, such as middle-ear muscle activity (MEMA), as a consequence of an increase of middle-ear reflex frequency during pre-sleep wake. Ten subjects were studied in three consecutive nights (one adaptation, one baseline, one experimental). In the experimental night, subjects underwent a 2-h pure-tone (1000 Hz, 90 dB SPL) auditory stimulation and MEMA was monitored every 15 min; noise exposure during daytime was also controlled. Results show that MEMA frequency during REM sleep significantly decreased during the experimental nights compared with baseline nights, while each sleep variable as well as mean daily auditory input did not present any significant difference between baseline and experimental nights. Results suggest that the complementary relationship between wake and REM sleep is not bounded to oculomotor activity, but it may also be extended at least to middle-ear muscle phasic activity. Received: 30 April 1999 / Accepted: 14 September 1999     

Physiological time structure of the tibialis anterior motor activity during sleep in mice,rats and humans

The validation of rodent models for restless legs syndrome (Willis–Ekbom disease) and periodic limb movements during sleep requires knowledge of physiological limb motor activity during sleep in rodents. This study aimed to determine the physiological time structure of tibialis anterior activity during sleep in mice and rats, and compare it with that of healthy humans. Wild‐type mice (n = 9) and rats (n = 8) were instrumented with electrodes for recording the electroencephalogram and electromyogram of neck muscles and both tibialis anterior muscles. Healthy human subjects (31 ± 1 years, n = 21) underwent overnight polysomnography. An algorithm for automatic scoring of tibialis anterior electromyogram events of mice and rats during non‐rapid eye movement sleep was developed and validated. Visual scoring assisted by this algorithm had inter‐rater sensitivity of 92–95% and false‐positive rates of 13–19% in mice and rats. The distribution of the time intervals between consecutive tibialis anterior electromyogram events during non‐rapid eye movement sleep had a single peak extending up to 10 s in mice, rats and human subjects. The tibialis anterior electromyogram events separated by intervals <10 s mainly occurred in series of two‐three events, their occurrence rate in humans being lower than in mice and similar to that in rats. In conclusion, this study proposes reliable rules for scoring tibialis anterior electromyogram events during non‐rapid eye movement sleep in mice and rats, demonstrating that their physiological time structure is similar to that of healthy young human subjects. These results strengthen the basis for translational rodent models of periodic limb movements during sleep and restless legs syndrome/Willis–Ekbom disease.     

A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders

Human studies have shown that a reduction of 5-HT transporter (SERT) increases the vulnerability for anxiety and depression. Moreover, women are more vulnerable to develop depression and anxiety disorders than men. For that reason we hypothesized that homozygous 5-HT transporter knockout rat (SERT(-/-)) models, especially female, are valuable and reliable animal models for humans with an increased vulnerability for anxiety- and depression-related disorders. As rats are extensively used in neuroscience research, we used the unique 5-HT transporter knockout rat, that was recently generated using N-ethyl-N-nitrosurea (ENU) -driven mutagenesis, to test this hypothesis. Behavioral testing revealed that male and female SERT(-/-) rats spent less time in the center of the open field and spent less time on the open arm of the elevated plus maze compared with wild-type 5-HT transporter knockout rats (SERT(+/+)). In the novelty suppressed feeding test, only male SERT(-/-) rats showed a higher latency before starting to eat in a bright novel arena compared with SERT(+/+) controls. Both male and female SERT(-/-) rats showed a higher escape latency from their home cage than SERT(+/+) littermates. Moreover, SERT(-/-) rats were less mobile in the forced swim test, and sucrose consumption was reduced in SERT(-/-) rats relative to SERT(+/+) rats. Both effects were sex-independent. Neurochemically, basal extracellular 5-HT levels were elevated to a similar extent in male and female SERT(-/-) rats, which was not influenced by the selective 5-HT reuptake inhibitor citalopram. 5-HT immunostaining revealed no difference between SERT(+/+) and SERT(-/-) rats in the dorsal raphe nuclei, in both males and females. These findings demonstrate that SERT(-/-) rats show anxiety and depression-related behavior, independent of sex. Genetic inactivation of the SERT has apparently such a great impact on behavior, that hardly any differences are found between male and female rats. This knockout rat model may provide a valuable model to study anxiety- and depression-related disorders in male and female rats.     

Functional connectivity in slow-wave sleep: identification of synchronous cortical activity during wakefulness and sleep using time series analysis of electroencephalographic data

Sleep is a behavioral state ideal for studying functional connectivity because it minimizes many sources of between-subject variability that confound waking analyses. This is particularly important for potential connectivity studies in mental illness where cognitive ability, internal milieu and active psychotic symptoms can vary widely across subjects. We, therefore, sought to adapt techniques applied to magnetoencephalography for use in high-density electroencephalography (EEG), the gold-standard in brain-recording methods during sleep. Autoregressive integrative moving average modeling was used to reduce spurious correlations between recording sites (electrodes) in order to identify functional networks. We hypothesized that identified network characteristics would be similar to those found with magnetoencephalography, and would demonstrate sleep stage-related differences in a control population. We analysed 60-s segments of low-artifact data from seven healthy human subjects during wakefulness and sleep. EEG analysis of eyes-closed wakefulness revealed widespread nearest-neighbor positive synchronous interactions, similar to magnetoencephalography, though less consistent across subjects. Rapid eye movement sleep demonstrated positive synchronous interactions akin to wakefulness but weaker. Slow-wave sleep (SWS), instead, showed strong positive interactions in a large left fronto-temporal-parietal cluster markedly more consistent across subjects. Comparison of connectivity from early SWS to SWS from a later sleep cycle indicated sleep-related reduction in connectivity in this region. The consistency of functional connectivity during SWS within and across subjects suggests this may be a promising technique for comparing functional connectivity between mental illness and health.     

Modulation of TASK-1/3 channels at the hypoglossal motoneuron pool and effects on tongue motor output and responses to excitatory inputs in vivo: implications for strategies for obstructive sleep apnea pharmacotherapy

Obstructive sleep apnea (OSA) occurs exclusively during sleep due to reduced tongue motor activity. Withdrawal of excitatory inputs to the hypoglossal motor nucleus (HMN) from wake to sleep contributes to this reduced activity. Several awake–active neurotransmitters with inputs to the HMN (e.g. serotonin [5-HT]) inhibit K⁺ leak mediated by TASK-1/3 channels on hypoglossal motoneurons, leading to increased neuronal activity in vitro. We hypothesize that TASK channel inhibition at the HMN will increase tongue muscle activity in vivo and modulate responses to 5-HT. We first microperfused the HMN of anesthetized rats with TASK channel inhibitors: doxapram (75 μM, n = 9), A1899 (25 μM, n = 9), ML365 (25 μM, n = 9), acidified artificial cerebrospinal fluid (ACSF, pH = 6.25, n = 9); and a TASK channel activator terbinafine (50 μM, n = 9); all with and without co-applied 5-HT (10 mM). 5-HT alone at the HMN increased tongue motor activity (202.8% ± 45.9%, p < 0.001). However, neither the TASK channel inhibitors, nor activator, at the HMN changed baseline tongue activity (p > 0.716) or responses to 5-HT (p > 0.127). Tonic tongue motor responses to 5-HT at the HMN were also not different (p > 0.05) between ChAT-Cre:TASK^f/f mice (n = 8) lacking TASK-1/3 channels on cholinergic neurons versus controls (n = 10). In freely behaving rats (n = 9), microperfusion of A1899 into the HMN increased within-breath phasic tongue motor activity in wakefulness only (p = 0.005) but not sleep, with no effects on tonic activity across all sleep–wake states. Together, the findings suggest robust maintenance of tongue motor activity despite various strategies for TASK channel manipulation targeting the HMN in vivo, and thus currently do not support this target and direction for potential OSA pharmacotherapy.     

The key role of insomnia and sleep loss in the dysregulation of multiple systems involved in mood disorders: A proposed model

Mood disorders are amongst the most prevalent and severe disorders worldwide, with a tendency to be recurrent and disabling. Although multiple mechanisms have been hypothesized to be involved in their pathogenesis, just a few integrative theoretical frameworks have been proposed and have yet to integrate comprehensively all available findings. As such, a comprehensive framework would be quite useful from a clinical and therapeutic point of view in order to identify elements to evaluate and target in the clinical practice. Because conditions of sleep loss, which include reduced sleep duration and insomnia, are constant alterations in mood disorders, the aim of this paper was to review the literature on their potential role in the pathogenesis of mood disorders and to propose a novel theoretical model. According to this hypothesis, sleep should be considered the main regulator of several systems and processes whose dysregulation is involved in the pathogenesis of mood disorders. The model may help explain why sleep disturbances are so strikingly linked to mood disorders, and underscores the need to evaluate, assess and target sleep disturbances in clinical practice, as a priority, in order to prevent and treat mood disorders.     

Nuclear organization of some immunohistochemically identifiable neural systems in two species of the Euarchontoglires: A Lagomorph,Lepus capensis,and a Scandentia,Tupaia belangeri

The present study describes the organization of the nuclei of the cholinergic, catecholaminergic, serotonergic and orexinergic systems in the brains of two members of Euarchontoglires, Lepus capensis and Tupaia belangeri. The aim of the present study was to investigate the nuclear complement of these neural systems in comparison to previous studies on Euarchontoglires and generally with other mammalian species. Brains were coronally sectioned and immunohistochemically stained with antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin and orexin-A. The majority of nuclei revealed in the current study were similar between the species investigated and to mammals generally, but certain differences in the nuclear complement highlight potential phylogenetic interrelationships within the Euarchontoglires and across mammals. In the northern tree shrew the nucleus of the trapezoid body contained neurons immunoreactive to the choline acetyltransferase antibody with some of these neurons extending into the lamellae within the superior olivary nuclear complex (SON). The cholinergic nature of the neurons of this nucleus, and the extension of cholinergic neurons into the SON, has not been noted in any mammal studied to date. In addition, cholinergic neurons forming the medullary tegmental field were also present in the northern tree shrew. Regarding the catecholaminergic system, the cape hare presented with the rodent specific rostral dorsal midline medullary nucleus (C3), and the northern tree shrew lacked both the ventral and dorsal divisions of the anterior hypothalamic group (A15v and A15d). Both species were lacking the primate/megachiropteran specific compact portion of the locus coeruleus complex (A6c). The nuclei of the serotonergic and orexinergic systems of both species were similar to those seen across most Eutherian mammals. Our results lend support to the monophyly of the Glires, and more broadly suggest that the megachiropterans are more closely related to the primates than are any other members of Euarchontoglires studied to date.     

Nuclear organization of cholinergic,catecholaminergic, serotonergic and orexinergic systems in the brain of the Tasmanian devil (Sarcophilus harrisii)

This study investigated the nuclear organization of four immunohistochemically identifiable neural systems (cholinergic, catecholaminergic, serotonergic and orexinergic) within the brains of three male Tasmanian devils (Sarcophilus harrisii), which had a mean brain mass of 11.6 g. We found that the nuclei generally observed for these systems in other mammalian brains were present in the brain of the Tasmanian devil. Despite this, specific differences in the nuclear organization of the cholinergic, catecholaminergic and serotonergic systems appear to carry a phylogenetic signal. In the cholinergic system, only the dorsal hypothalamic cholinergic nucleus could be observed, while an extra dorsal subdivision of the laterodorsal tegmental nucleus and cholinergic neurons within the gelatinous layer of the caudal spinal trigeminal nucleus were observed. Within the catecholaminergic system the A4 nucleus of the locus coeruleus complex was absent, as was the caudal ventrolateral serotonergic group of the serotonergic system. The organization of the orexinergic system was similar to that seen in many mammals previously studied. Overall, while showing strong similarities to the organization of these systems in other mammals, the specific differences observed in the Tasmanian devil reveal either order specific, or class specific, features of these systems. Further studies will reveal the extent of change in the nuclear organization of these systems in marsupials and how these potential changes may affect functionality.