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Torpor is a state used by several mammals to survive harsh winters and avoid predation, characterized by a drastic reduction in metabolic rate followed by a decrease in body temperature, heart rate, and many physiological variables. During torpor, all organs and systems must adapt to the new low-energy expenditure conditions to preserve physiological homeostasis. These adaptations may be exploited in a translational perspective in several fields. Recently, many features of torpor were shown to be mimicked in non-hibernators by the inhibition of neurons within the brainstem region of the Raphe Pallidus. The physiological resemblance of this artificial state, called synthetic torpor, with natural torpor has so far been described only in physiological terms, but no data have been shown regarding the induced morphological changes. Here, we show the first description of the ultrastructural changes in the liver, kidney, lung, skeletal muscle, and testis induced by a 6-hours inhibition of Raphe Pallidus neurons in a non-hibernating species, the rat. [ABSTRACT FROM AUTHOR]

The Raphe Pallidus (RPa) is a brainstem nucleus containing sympathetic premotor neurons that control thermogenesis and modulate cardiovascular function. It receives inputs from various hypothalamic areas, including the Lateral Hypothalamus (LH), a heterogeneous region intricately involved in several autonomic and behavioral functions. A key subpopulation of neurons in the LH expresses orexin/hypocretin, a neuropeptide which is crucially involved in the regulation of the wake-sleep states and feeding behavior. The RPa receives orexinergic projections from the LH and orexinergic signalling in the RPa has been shown to enhance thermogenesis in the anaesthetized rat, but only in the presence of an already existing thermogenic drive, without significantly affecting cardiovascular function. The present work was aimed at exploring the effects on thermoregulation and autonomic function and the possible role in the modulation of the wake-sleep states and feeding behavior of orexin injection in the RPa in the free-behaving rat. In order to assess the influence of an already present thermogenic drive on orexinergic signalling in the RPa, animals were studied at three different ambient temperatures (Ta, 10°C, 24°C, and 32°C). We found that orexin injection into the RPa variably affected the wake-sleep states, autonomic functions, motor activity, and feeding behavior, at the different Tas. In particular, in the first post-injection hour, we observed an increase in wakefulness, which was large at Ta 24°C and Ta 10°C and rather mild at Ta 32°C. Deep brain temperature was increased by orexin injection at Ta 10°C, but not at either Ta 24°C or Ta 32°C. Moreover, an increase in mean arterial blood pressure occurred at Ta 24°C, which was probably masked by the high baseline levels at Ta 10°C and was completely absent at Ta 32°C. Finally, an enhancement in feeding behavior was observed at Ta 24°C and 10°C only. In accordance with what observed in anaesthetized rats, orexinergic signalling in the RPa seems to be ineffective in the absence of any thermogenic drive. Moreover, the effects observed on the wake-sleep states and feeding behavior introduce the RPa as a novel player in the central neural network promoting wakefulness and feeding. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Although behavioural defensive responses have been recorded several times in both laboratory and natural habitats, their neural mechanisms have seldom been investigated. To explore how chemical, water-borne cues are conveyed to the forebrain and instruct behavioural responses in anuran larvae, we conditioned newly hatched agile frog tadpoles using predator olfactory cues, specifically either native odonate larvae or alien crayfish kairomones. We expected chronic treatments to influence the basal neuronal activity of the tadpoles' mitral cells and alter their sensory neuronal connections, thereby impacting information processing. Subsequently, these neurons were acutely perfused, and their responses were compared with the defensive behaviour of tadpoles previously conditioned and exposed to the same cues. Tadpoles conditioned with odonate cues differed in both passive and active cell properties compared to those exposed to water (controls) or crayfish cues. The observed upregulation of membrane conductance and increase in both the number of active synapses and receptor density at the postsynaptic site are believed to have enhanced their responsiveness to external stimuli. Odonate cues also affected the resting membrane potential and firing rate of mitral cells during electrophysiological patch-clamp recordings, suggesting a rearrangement of the repertoire of voltage-dependent conductances expressed in cell membranes. These recorded neural changes may modulate the induction of an action potential and transmission of information. Furthermore, the recording of neural activity indicated that the lack of defensive responses towards non-native predators is due to the non-recognition of their olfactory cues. [ABSTRACT FROM AUTHOR]

Background: The hyperphosphorylation of tau protein (PPtau) in the brain is the main pathophysiological marker of tauopathies. Recently was found that when induced by a "synthetic torpor" (ST)1 condition (induced on rats), PPtau accumulations is reversible, as observed in hibernators2. Thus, ST uncover a latent physiological mechanism able to cope with PPtau and not specifically evolved with hibernation. Aim of the present work was to describe it. Methods: We induced ST as already reported2 on 12 Sprague‐Dawley rats. Hippocampal and plasma samples were collected at the following experimental conditions: nadir of hypothermia (N); early recovery (ER), as soon as animals reached normothermia following N; 6h following ER (R6). Control (C) animals were also included. Levels of AT8 (p[S020/T205]‐tau), p[S9]‐GSK3β (inhibited form of the main kinase targeting tau) and plasma melatonin were determined. To better understand in vivo experimental results, we performed in silico simulations of melatonin‐tubulin interactions3. Results: Figure 1 shows, at N, a huge amount of AT8 and high levels of p[S9]‐GSK3β and melatonin in respect to C. All factors returned to normal at R6. These paradoxical results (i.e. the coexistence of high levels of PPtau and p[S9]‐GSK3β) could be interpreted considering the destabilization of microtubules (MTs) induced by hypothermia as the main trigger of the whole process, then eliciting a neuroprotective physiological response mediated by melatonin, also interacting with MTs. To sustain this hypothesis, we also provide computational analysis of the microtubule stability as a function of temperature and other factors, such as melatonin binding. The molecular docking simulation shows that melatonin did not bind to 1sa0 structure, but it binds to one site of 1jff structure on the α‐tubulin monomer (Figure 2). This is further elucidated using a molecular fingerprint representation (Figure 3), showing the binding site of melatonin with respect to those well‐known binding locations. Conclusions: Our results could pave the way for an effective new strategy to contrast tauopathies, with next‐step studies aimed to pharmacologically interacting with this process at physiological temperature. References: (1) Luppi et al. Front Neuroanat 2019, 13:57; (2) Stieler et al. PLoS One 2011, 6: e14530. 3Craddock, et al. Sci Reports 2017, 7:1. [ABSTRACT FROM AUTHOR]