Ultrasonic vocalisations during rapid eye movement sleep in the rat.

Rats are known to use a 22-kHz ultrasonic vocalisation as a distress call to warn of danger to other members of their group. We monitored 22-kHz ultrasonic vocalisation emissions in rats (lean and obese) as part of a sleep deprivation study to detect the eventual presence of stress during the procedure. Unexpectedly, we detected ultrasonic vocalisation emission during rapid eye movement (REM) sleep, but not during non-REM (NREM) sleep, in all the rats. The event occurs during the expiratory phase and can take place singularly or as a train. No difference was detected in the number or duration of these events in lean versus obese rats, during the light versus the dark period, and after sleep deprivation. As far as we know, this is the first report showing that rats can vocalise during REM sleep.

Neurogenic Fever after Subarachnoid Hemorrhage in Animal Models: A Systematic Review.

The observation of neurogenic fever resulting from subarachnoid hemorrhage (SAH) in animal models is a useful tool for the interpretation of its pathophysiology in humans, which is still a major challenge in the management of neurocritical patients. This systematic review aims to identify the prognostic factors and pathophysiological elements that determine the onset of neurogenic fever and its severity in animal models. In addition, our study aims to analyze which pharmacological treatments are most effective. All the articles available in Pubmed, Embase, and the Biological Science Collection until August 2021 concerning in vivo experimental studies on SAH animal models, including full texts and abstracts written in English and Italian, were considered. The risk of bias was assessed with SYRCLE's Risk of Bias tool. In total, 81 records were retrieved; after excluding duplicates, 76 records were potentially relevant. A total of 64 articles was excluded after title and abstract screening. The remaining 12 studies were evaluated as full texts, and 6 other studies were excluded (SAH-induced animal studies without a body temperature assessment). In one study, body temperature was measured after SAH induction, but the authors did not report temperature recording. Therefore, only five studies met the search criteria. The high methodological heterogeneity (different animal species, different temperature measurement methods, and different methods of the induction of bleeding) prevented meta-analysis. Synthesis methodology without meta-analysis (SWiM) was used for data analysis. The total number of animals used as controls was 87 (23 rabbits, 32 mice, and 32 rats), while there were 130 animals used as interventions (54 rabbits, 44 mice, and 32 rats). The presence of blood in the subarachnoid space, particularly red blood cells, is responsible for neurogenic fever; the role of hemoglobin is unclear. The mechanism is apparently not mediated by prostaglandins. The autonomic nervous system innervating brown adipose tissue is undoubtedly implicated in the onset of neurogenic fever. The activation of the central adenosine-1 receptor is effective in controlling the temperature of animals with neurogenic fever (by inhibiting thermogenesis of brown adipose tissue).

Loss of Snord116 alters cortical neuronal activity in mice: a preclinical investigation of Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder that is characterized by metabolic alteration and sleep abnormalities mostly related to rapid eye movement (REM) sleep disturbances. The disease is caused by genomic imprinting defects that are inherited through the paternal line. Among the genes located in the PWS region on chromosome 15 (15q11-q13), small nucleolar RNA 116 (Snord116) has been previously associated with intrusions of REM sleep into wakefulness in humans and mice. Here, we further explore sleep regulation of PWS by reporting a study with PWScrm+/p- mouse line, which carries a paternal deletion of Snord116. We focused our study on both macrostructural electrophysiological components of sleep, distributed among REMs and nonrapid eye movements. Of note, here, we study a novel electroencephalography (EEG) graphoelements of sleep for mouse studies, the well-known spindles. EEG biomarkers are often linked to the functional properties of cortical neurons and can be instrumental in translational studies. Thus, to better understand specific properties, we isolated and characterized the intrinsic activity of cortical neurons using in vitro microelectrode array. Our results confirm that the loss of Snord116 gene in mice influences specific properties of REM sleep, such as theta rhythms and, for the first time, the organization of REM episodes throughout sleep-wake cycles. Moreover, the analysis of sleep spindles present novel specific phenotype in PWS mice, indicating that a new catalog of sleep biomarkers can be informative in preclinical studies of PWS.

Autonomic effects induced by pharmacological activation and inhibition of Raphe Pallidus neurons in anaesthetized adult pigs.

The Raphe Pallidus (RPa) is a region of the brainstem that was shown to modulate the sympathetic outflow to many tissues and organs involved in thermoregulation and energy expenditure. In rodents, the pharmacological activation of RPa neurons was shown to increase the activity of the brown adipose tissue, heart rate, and expired CO2 , whereas their inhibition was shown to induce cutaneous vasodilation and a state of hypothermia that, when prolonged, leads to a state resembling torpor referred to as synthetic torpor. If translatable to humans, this synthetic torpor-inducing procedure would be advantageous in many clinical settings. A first step to explore such translatability, has been to verify whether the neurons within the RPa play the same role described for rodents in a larger mammal such as the pig. In the present study, we show that the physiological responses inducible by the pharmacological stimulation of RPa neurons are very similar to those observed in rodents. Injection of the GABAA agonist GABAzine in the RPa induced an increase in heart rate (from 99 to 174 bpm), systolic (from 87 to 170 mm Hg) and diastolic (from 51 to 98 mm Hg) arterial pressure, and end-tidal CO2 (from 49 to 62 mm Hg). All these changes were reversed by the injection in the same area of the GABAA agonist muscimol. These results support the possibility for RPa neurons to be a key target in the research for a safe and effective procedure for the induction of synthetic torpor in humans.

c-Fos expression in the limbic thalamus following thermoregulatory and wake-sleep changes in the rat.

A cellular degeneration of two thalamic nuclei belonging to the "limbic thalamus", i.e., the anteroventral (AV) and mediodorsal (MD) nuclei, has been shown in patients suffering from Fatal Familial Insomnia (FFI), a lethal prion disease characterized by autonomic activation and severe insomnia. To better assess the physiological role of these nuclei in autonomic and sleep regulation, c-Fos expression was measured in rats during a prolonged exposure to low ambient temperature (Ta, - 10 °C) and in the first hours of the subsequent recovery period at normal laboratory Ta (25 °C). Under this protocol, the thermoregulatory and autonomic activation led to a tonic increase in waking and to a reciprocal depression in sleep occurrence, which was more evident for REM sleep. These effects were followed by a clear REM sleep rebound and by a rebound of Delta power during non-REM sleep in the following recovery period. In the anterior thalamic nuclei, c-Fos expression was (1) larger during the activity rather than the rest period in the baseline; (2) clamped at a level in-between the normal daily variation during cold exposure; (3) not significantly affected during the recovery period in comparison to the time-matched baseline. No significant changes were observed in either the MD or the paraventricular thalamic nucleus, which is also part of the limbic thalamus. The observed changes in the activity of the anterior thalamic nuclei appear, therefore, to be more specifically related to behavioral activation than to autonomic or sleep regulation.

Hibernation and Radioprotection: Gene Expression in the Liver and Testicle of Rats Irradiated under Synthetic Torpor.

Hibernation has been proposed as a tool for human space travel. In recent years, a procedure to induce a metabolic state known as "synthetic torpor" in non-hibernating mammals was successfully developed. Synthetic torpor may not only be an efficient method to spare resources and reduce psychological problems in long-term exploratory-class missions, but may also represent a countermeasure against cosmic rays. Here we show the preliminary results from an experiment in rats exposed to ionizing radiation in normothermic conditions or synthetic torpor. Animals were irradiated with 3 Gy X-rays and organs were collected 4 h after exposure. Histological analysis of liver and testicle showed a reduced toxicity in animals irradiated in torpor compared to controls irradiated at normal temperature and metabolic activity. The expression of ataxia telangiectasia mutated (ATM) in the liver was significantly downregulated in the group of animal in synthetic torpor. In the testicle, more genes involved in the DNA damage signaling were downregulated during synthetic torpor. These data show for the first time that synthetic torpor is a radioprotector in non-hibernators, similarly to natural torpor in hibernating animals. Synthetic torpor can be an effective strategy to protect humans during long term space exploration of the solar system.

Sleepiness at the wheel across Europe: a survey of 19 countries.

The European Sleep Research Society aimed to estimate the prevalence, determinants and consequences of falling asleep at the wheel. In total, 12 434 questionnaires were obtained from 19 countries using an anonymous online questionnaire that collected demographic and sleep-related data, driving behaviour, history of drowsy driving and accidents. Associations were quantified using multivariate logistic regression. The average prevalence of falling asleep at the wheel in the previous 2 years was 17%. Among respondents who fell asleep, the median prevalence of sleep-related accidents was 7.0% (13.2% involved hospital care and 3.6% caused fatalities). The most frequently perceived reasons for falling asleep at the wheel were poor sleep in the previous night (42.5%) and poor sleeping habits in general (34.1%). Falling asleep was more frequent in the Netherlands [odds ratio = 3.55 (95% confidence interval: 1.97; 6.39)] and Austria [2.34 (1.75; 3.13)], followed by Belgium [1.52 (1.28; 1.81)], Portugal [1.34 (1.13, 1.58)], Poland [1.22 (1.06; 1.40)] and France [1.20 (1.05; 1.38)]. Lower odds were found in Croatia [0.36 (0.21; 0.61)], Slovenia [0.62 (0.43; 0.89)] and Italy [0.65 (0.53; 0.79)]. Individual determinants of falling asleep were younger age; male gender [1.79 (1.61; 2.00)]; driving ≥20 000 km year [2.02 (1.74; 2.35)]; higher daytime sleepiness [7.49 (6.26; 8.95)] and high risk of obstructive sleep apnea syndrome [3.48 (2.78; 4.36) in men]. This Pan European survey demonstrates that drowsy driving is a major safety hazard throughout Europe. It emphasizes the importance of joint research and policy efforts to reduce the burden of sleepiness at the wheel for European drivers.

Wake-sleep, thermoregulatory, and autonomic effects of cholinergic activation of the lateral hypothalamus in the rat: a pilot study.

A major role in the wake-promoting effects of the activation of the lateral hypothalamus (LH) has been ascribed to a population of orexin (ORX)-containing neurons that send projections to central areas which regulate Wake-Sleep and autonomic function. Since, in the rat, a substantial amount of ORX neurons receive cholinergic projections from cells involved in Wake-Sleep regulation, the aim of this study was to assess the role played by LH cholinoceptive cells in Wake-Sleep and autonomic regulations. To this end, the effects of a microinjection of the cholinergic agonist Carbachol (CBL) into the LH were compared to those obtained through the activation of a wider cell population by the microinjection of the GABAA antagonist GABAzine (GBZ). The results of this pilot study showed that both drugs elicited the same behavioral and autonomic effects, those caused by GBZ being larger and longer-lasting than those following administration of CBL. Briefly, wakefulness was enhanced and sleep was depressed, and brain temperature and heart rate consistently increased, while mean arterial pressure showed only a mild increment. Surprisingly, the administration of the drug vehicle (SAL) elicited a similar pattern of Wake-Sleep effects which, although much smaller, were sufficient to mask any statistical significance between treatment and control data. In conclusion, the results of this work show that the arousal elicited by LH disinhibition by GABAzine is concomitant with autonomic responses set by the intervention of cold-defense mechanisms. Since the same response is elicited at a lower level by CBL administration, the hypothesis of an involvement of cholinoceptive ORX neurons in its generation is discussed.

The inhibition of neurons in the central nervous pathways for thermoregulatory cold defense induces a suspended animation state in the rat.

The possibility of inducing a suspended animation state similar to natural torpor would be greatly beneficial in medical science, since it would avoid the adverse consequence of the powerful autonomic activation evoked by external cooling. Previous attempts to systemically inhibit metabolism were successful in mice, but practically ineffective in nonhibernators. Here we show that the selective pharmacological inhibition of key neurons in the central pathways for thermoregulatory cold defense is sufficient to induce a suspended animation state, resembling natural torpor, in a nonhibernator. In rats kept at an ambient temperature of 15°C and under continuous darkness, the prolonged inhibition (6 h) of the rostral ventromedial medulla, a key area of the central nervous pathways for thermoregulatory cold defense, by means of repeated microinjections (100 nl) of the GABA(A) agonist muscimol (1 mm), induced the following: (1) a massive cutaneous vasodilation; (2) drastic drops in deep brain temperature (reaching a nadir of 22.44 ± 0.74°C), heart rate (from 440 ± 13 to 207 ± 12 bpm), and electroencephalography (EEG) power; (3) a modest decrease in mean arterial pressure; and (4) a progressive shift of the EEG power spectrum toward slow frequencies. After the hypothermic bout, all animals showed a massive increase in NREM sleep Delta power, similarly to that occurring in natural torpor. No behavioral abnormalities were observed in the days following the treatment. Our results strengthen the potential role of the CNS in the induction of hibernation/torpor, since CNS-driven changes in organ physiology have been shown to be sufficient to induce and maintain a suspended animation state.

Provocative motion causes fall in brain temperature and affects sleep in rats.

Neural substrate of nausea is poorly understood, contrasting the wealth of knowledge about the emetic reflex. One of the reasons for this knowledge deficit is limited number and face validity of animal models of nausea. Our aim was to search for new physiological correlates of nausea in rats. Specifically, we addressed the question whether provocative motion (40-min rotation at 0.5 Hz) affects sleep architecture, brain temperature, heart rate (HR) and arterial pressure. Six adult male Sprague­Dawley rats were instrumented for recordings of EEG, nuchal electromyographic, hypothalamic temperature and arterial pressure. Provocative motion had the following effects: (1) total abolition of REM sleep during rotation and its substantial reduction during the first hour post-rotation (from 20 ± 3 to 5 ± 1.5%); (2) reduction in NREM sleep, both during rotation (from 57 ± 6 to 19 ± 5%) and during the first hour post-rotation (from 56 ± 3 to 41 ± 9%); (3) fall in the brain temperature (from 37.1 ± 0.1 to 36.0 ± 0.1 °C); and (4) reduction in HR (from 375 ± 6 to 327 ± 7 bpm); arterial pressure was not affected. Ondansetron, a 5-HT3 antagonist, had no major effect on all observed parameters during both baseline and provocative motion. We conclude that in rats, provocative motion causes prolonged arousing effects, however without evidence of sympathetic activation that usually accompanies heightened arousal. Motion induced fall in the brain temperature complements and extends our previous observations in rats and suggests that similar to humans, provocative motion triggers coordinated thermoregulatory response, leading to hypothermia in this species.

Fluorescent Neuronal Cells v2: multi-task, multi-format annotations for deep learning in microscopy.

Fluorescent Neuronal Cells v2 is a collection of fluorescence microscopy images and the corresponding ground-truth annotations, designed to foster innovative research in the domains of Life Sciences and Deep Learning. This dataset encompasses three image collections wherein rodent neuronal cell nuclei and cytoplasm are stained with diverse markers to highlight their anatomical or functional characteristics. Specifically, we release 1874 high-resolution images alongside 750 corresponding ground-truth annotations for several learning tasks, including semantic segmentation, object detection and counting. The contribution is two-fold. First, thanks to the variety of annotations and their accessible formats, we anticipate our work will facilitate methodological advancements in computer vision approaches for segmentation, detection, feature extraction, unsupervised and self-supervised learning, transfer learning, and related areas. Second, by enabling extensive exploration and benchmarking, we hope Fluorescent Neuronal Cells v2 will catalyze breakthroughs in fluorescence microscopy analysis and promote cutting-edge discoveries in life sciences.

Corrigendum: Synthetic torpor triggers a regulated mechanism in the rat brain, favoring the reversibility of Tau protein hyperphosphorylation.

[This corrects the article DOI: 10.3389/fphys.2023.1129278.].

Synthetic torpor triggers a regulated mechanism in the rat brain, favoring the reversibility of Tau protein hyperphosphorylation.

Introduction: Hyperphosphorylated Tau protein (PPTau) is the hallmark of tauopathic neurodegeneration. During "synthetic torpor" (ST), a transient hypothermic state which can be induced in rats by the local pharmacological inhibition of the Raphe Pallidus, a reversible brain Tau hyperphosphorylation occurs. The aim of the present study was to elucidate the - as yet unknown - molecular mechanisms underlying this process, at both a cellular and systemic level. Methods: Different phosphorylated forms of Tau and the main cellular factors involved in Tau phospho-regulation were assessed by western blot in the parietal cortex and hippocampus of rats induced in ST, at either the hypothermic nadir or after the recovery of euthermia. Pro- and anti-apoptotic markers, as well as different systemic factors which are involved in natural torpor, were also assessed. Finally, the degree of microglia activation was determined through morphometry. Results: Overall, the results show that ST triggers a regulated biochemical process which can dam PPTau formation and favor its reversibility starting, unexpectedly for a non-hibernator, from the hypothermic nadir. In particular, at the nadir, the glycogen synthase kinase-ß was largely inhibited in both regions, the melatonin plasma levels were significantly increased and the antiapoptotic factor Akt was significantly activated in the hippocampus early after, while a transient neuroinflammation was observed during the recovery period. Discussion: Together, the present data suggest that ST can trigger a previously undescribed latent and regulated physiological process, that is able to cope with brain PPTau formation.

Sleep deprivation soon after recovery from synthetic torpor enhances tau protein dephosphorylation in the rat brain.

Neuronal Tau protein hyperphosphorylation (PPtau) is a hallmark of tauopathic neurodegeneration. However, a reversible brain PPtau occurs in mammals during either natural or "synthetic" torpor (ST), a transient deep hypothermic state that can be pharmacologically induced in rats. Since in both conditions a high sleep pressure builds up during the regaining of euthermia, the aim of this work was to assess the possible role of post-ST sleep in PPtau dephosphorylation. Male rats were studied at the hypothermic nadir of ST, and 3-6 h after the recovery of euthermia, after either normal sleep (NS) or total sleep deprivation (SD). The effects of SD were studied by assessing: (i) deep brain temperature (Tb); (ii) immunofluorescent staining for AT8 (phosphorylated Tau) and Tau-1 (non-phosphorylated Tau), assessed in 19 brain structures; (iii) different phosphorylated forms of Tau and the main cellular factors involved in Tau phospho-regulation, including pro- and anti-apoptotic markers, assessed through western blot in the parietal cortex and hippocampus; (iv) systemic factors which are involved in natural torpor; (v) microglia activation state, by considering morphometric variations. Unexpectedly, the reversibility of PPtau was more efficient in SD than in NS animals, and was concomitant with a higher Tb, higher melatonin plasma levels, and a higher frequency of the microglia resting phenotype. Since the reversibility of ST-induced PPtau was previously shown to be driven by a latent physiological molecular mechanism triggered by deep hypothermia, short-term SD soon after the regaining of euthermia seems to boost the possible neuroprotective effects of this mechanism.

Mitochondrial respiration in rats during hypothermia resulting from central drug administration.

The ability to induce a hypothermia resembling that of natural torpor would be greatly beneficial in medical and non-medical fields. At present, two procedures based on central nervous pharmacological manipulation have been shown to be effective in bringing core body temperature well below 30 °C in the rat, a non-hibernator: the first, based on the inhibition of a key relay in the central thermoregulatory pathway, the other, based on the activation of central adenosine A1 receptors. Although the role of mitochondria in the activation and maintenance of torpor has been extensively studied, no data are available for centrally induced hypothermia in non-hibernators. Thus, in the present work the respiration rate of mitochondria in the liver and in the kidney of rats following the aforementioned hypothermia-inducing treatments was studied. Moreover, to have an internal control, the same parameters were assessed in a well-consolidated model, i.e., mice during fasting-induced torpor. Our results show that state 3 respiration rate, which significantly decreased in the liver of mice, was unchanged in rats. An increase of state 4 respiration rate was observed in both species, although it was not statistically significant in rats under central adenosine stimulation. Also, a significant decrease of the respiratory control ratio was detected in both species. Finally, no effects were detected in kidney mitochondria in both species. Overall, in these hypothermic conditions liver mitochondria of rats remained active and apparently ready to be re-activated to produce energy and warm up the cells. These findings can be interpreted as encouraging in view of the finalization of a translational approach to humans.

Thermoregulation and Sleep: Functional Interaction and Central Nervous Control.

Each of the wake-sleep states is characterized by specific changes in autonomic activity and bodily functions. The goal of such changes is not always clear. During non-rapid eye movement (NREM) sleep, the autonomic outflow and the activity of the endocrine system, the respiratory system, the cardiovascular system, and the thermoregulatory system seem to be directed at increasing energy saving. During rapid eye movement (REM) sleep, the goal of the specific autonomic and regulatory changes is unclear, since a large instability of autonomic activity and cardiorespiratory function is observed in concomitance with thermoregulatory changes, which are apparently non-functional to thermal homeostasis. Reciprocally, the activation of thermoregulatory responses under thermal challenges interferes with sleep occurrence. Such a double-edged and reciprocal interaction between sleep and thermoregulation may be favored by the fact that the central network controlling sleep overlaps in several parts with the central network controlling thermoregulation. The understanding of the central mechanism behind the interaction between sleep and thermoregulation may help to understand the functionality of thermoregulatory sleep-related changes and, ultimately, the function(s) of sleep. © 2021 American Physiological Society. Compr Physiol 11:1591-1604, 2021.

Be cool to be far: Exploiting hibernation for space exploration.

In mammals, torpor/hibernation is a state that is characterized by an active reduction in metabolic rate followed by a progressive decrease in body temperature. Torpor was successfully mimicked in non-hibernators by inhibiting the activity of neurons within the brainstem region of the Raphe Pallidus, or by activating the adenosine A1 receptors in the brain. This state, called synthetic torpor, may be exploited for many medical applications, and for space exploration, providing many benefits for biological adaptation to the space environment, among which an enhanced protection from cosmic rays. As regards the use of synthetic torpor in space, to fully evaluate the degree of physiological advantage provided by this state, it is strongly advisable to move from Earth-based experiments to 'in the field' tests, possibly on board the International Space Station.

Automating cell counting in fluorescent microscopy through deep learning with c-ResUnet.

Counting cells in fluorescent microscopy is a tedious, time-consuming task that researchers have to accomplish to assess the effects of different experimental conditions on biological structures of interest. Although such objects are generally easy to identify, the process of manually annotating cells is sometimes subject to fatigue errors and suffers from arbitrariness due to the operator's interpretation of the borderline cases. We propose a Deep Learning approach that exploits a fully-convolutional network in a binary segmentation fashion to localize the objects of interest. Counts are then retrieved as the number of detected items. Specifically, we introduce a Unet-like architecture, cell ResUnet (c-ResUnet), and compare its performance against 3 similar architectures. In addition, we evaluate through ablation studies the impact of two design choices, (i) artifacts oversampling and (ii) weight maps that penalize the errors on cells boundaries increasingly with overcrowding. In summary, the c-ResUnet outperforms the competitors with respect to both detection and counting metrics (respectively, [Formula: see text] score = 0.81 and MAE = 3.09). Also, the introduction of weight maps contribute to enhance performances, especially in presence of clumping cells, artifacts and confounding biological structures. Posterior qualitative assessment by domain experts corroborates previous results, suggesting human-level performance inasmuch even erroneous predictions seem to fall within the limits of operator interpretation. Finally, we release the pre-trained model and the annotated dataset to foster research in this and related fields.

Reversible Tau Phosphorylation Induced by Synthetic Torpor in the Spinal Cord of the Rat.

Tau is a key protein in neurons, where it affects the dynamics of the microtubule system. The hyperphosphorylation of Tau (PP-Tau) commonly leads to the formation of neurofibrillary tangles, as it occurs in tauopathies, a group of neurodegenerative diseases, including Alzheimer's. Hypothermia-related accumulation of PP-Tau has been described in hibernators and during synthetic torpor (ST), a torpor-like condition that has been induced in rats, a non-hibernating species. Remarkably, in ST PP-Tau is reversible and Tau de-phosphorylates within a few hours following the torpor bout, apparently not evolving into pathology. These observations have been limited to the brain, but in animal models of tauopathies, PP-Tau accumulation also appears to occur in the spinal cord (SpCo). The aim of the present work was to assess whether ST leads to PP-Tau accumulation in the SpCo and whether this process is reversible. Immunofluorescence (IF) for AT8 (to assess PP-Tau) and Tau-1 (non-phosphorylated Tau) was carried out on SpCo coronal sections. AT8-IF was clearly expressed in the dorsal horns (DH) during ST, while in the ventral horns (VH) no staining was observed. The AT8-IF completely disappeared after 6 h from the return to euthermia. Tau-1-IF disappeared in both DH and VH during ST, returning to normal levels during recovery. To shed light on the cellular process underlying the PP-Tau pattern observed, the inhibited form of the glycogen-synthase kinase 3ß (the main kinase acting on Tau) was assessed using IF: VH (i.e., in motor neurons) were highly stained mainly during ST, while in DH there was no staining. Since tauopathies are also related to neuroinflammation, microglia activation was also assessed through morphometric analyses, but no ST-induced microglia activation was found in the SpCo. Taken together, the present results show that, in the DH of SpCo, ST induces a reversible accumulation of PP-Tau. Since during ST there is no motor activity, the lack of AT8-IF in VH may result from an activity-related process at a cellular level. Thus, ST demonstrates a newly-described physiological mechanism that is able to resolve the accumulation of PP-Tau and apparently avoid the neurodegenerative outcome.

Hypothalamic osmoregulation is maintained across the wake-sleep cycle in the rat.

In different species, rapid eye movement sleep (REMS) is characterized by a thermoregulatory impairment. It has been postulated that this impairment depends on a general insufficiency in the hypothalamic integration of autonomic function. This study aims to test this hypothesis by assessing the hypothalamic regulation of body fluid osmolality during the different wake-sleep states in the rat. Arginine-vasopressin (AVP) plasma levels were determined following intracerebroventricular (ICV) infusions of artificial cerebrospinal fluid (aCSF), either isotonic or made hypertonic by the addition of NaCl at three different concentrations (125, 250 and 500 mM). Animals were implanted with a cannula within a lateral cerebral ventricle for ICV infusions and with electrodes for the recording of the electroencephalogram. ICV infusions were made in different animals during Wake, REMS or non-REM sleep (NREMS). The results show that ICV infusion of hypertonic aCSF during REMS induced an increase in AVP plasma levels that was not different from that observed during either Wake or NREMS. These results suggest that the thermoregulatory impairment that characterizes REMS does not depend on a general impairment in the hypothalamic control of body homeostasis.