Biology subjects

Torterolo, P.

Publications and source records attributed to Torterolo, P..

27 records · Page 2Linked to original sources

bioRxiv2021

Urethane Anesthesia Exhibits Neurophysiological Correlates of Unconsciousness and is Distinct from Sleep

Urethane is a general anesthetic widely used in animal research. It is unique among anesthetics because urethane anesthesia alternates between macroscopically distinct electrographic states: a slow-wave state that resembles NREM sleep (NREMure), and an activated state with features of both REM sleep and wakefulness (REMure). However, the relationship between urethane anesthesia and physiological sleep is still unclear. In this study, electroencephalography (EEG) and electromyography were recorded in chronically prepared rats during natural sleep-wake states and during urethane anesthesia. We subsequently analyzed the EEG signatures associated with the loss of consciousness and found that, in comparison to natural sleep-wake states, the power, coherence, directed connectivity and complexity of brain oscillations are distinct during urethane. We also demonstrate that both urethane states have clear EEG signatures of general anesthesia. Thus, despite superficial similarities that have led others to conclude that urethane is a model of sleep, the electrocortical traits of depressed and activated states during urethane anesthesia differ from physiological sleep states.

neuroscience↗

bioRxiv2021

OFF-periods reduce the complexity of neocortical activity during sleep

Complexity of electroencephalographic signals decreases during slow-wave sleep (SWS), however, the neural mechanism for this decrease remains elusive. Here, we show that this complexity reduction is caused by synchronous neuronal OFF-periods. We analyse in-vivo recordings from neocortical neuronal populations, finding that OFF-periods in SWS trap cortical dynamics, making the population activity more recurrent, deterministic, and less chaotic than during REM sleep or Wakefulness. Importantly, when we exclude OFF-periods, SWS becomes indistinguishable from Wakefulness or REM sleep. In fact, we show that spiking activity for all states has a universal scaling compatible with critical phenomena. We complement these results by a critical branching model that replicates our experimental findings, where we show that forcing OFF-periods to a percentage of neurons suffices to generate a decrease in complexity that replicates SWS.

neuroscience↗

bioRxiv2021

Role of hypocretin in the medial preoptic area in the regulation of sleep, maternal behavior and body temperature of lactating rats.

The hypocretins (HCRT), also known as orexin, includes two neuroexcitatory peptides, HCRT-1 and HCRT-2 (orexin A y B, respectively), synthesized by neurons located in the postero-lateral hypothalamus, whose projections and receptors are widely distributed throughout the brain, including the medial preoptic area (mPOA). HCRT have been associated with a wide range of physiological functions including sleep-wake cycle, maternal behavior and body temperature, all regulated by the mPOA. Previously we showed that HCRT in the mPOA facilitates certain active maternal behaviors, while the blockade of HCRT-R1 increased the time spent in nursing. As mother rats mainly sleep while they nurse, we hypothesize that HCRT in the mPOA of lactating rats reduce sleep and nursing, while the intra-mPOA administration of the dual orexin receptor antagonist (DORA) would generate the opposite effect. Therefore, the aim of this study was to determine the role of HCRT within the mPOA, in the regulation and integration of the sleep-wake cycle, maternal behavior and body temperature of lactating rats. To evaluate this idea, we assessed the sleep-wake states, maternal behavior and body temperature of lactating rats following microinjections of HCRT-1 (100 and 200 M) and DORA (5mM) into the mPOA. As expected, our data shows that HCRT-1 in mPOA promoted wakefulness and a slightly increase in body temperature, whereas DORA increased both NREM and REM sleep along with nursing and milk ejection. Taken together, our results strongly suggest that the reduction of the endogenous HCRT within the mPOA of lactating rats is important to promote sleep, nursing and milk ejection.

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bioRxiv2020

Glutamatergic neurons in the preoptic hypothalamus promote wakefulness, destabilize NREM sleep, suppress REM sleep, and regulate cortical dynamics

Clinical and experimental data from the last nine decades indicate that the preoptic area of the hypothalamus is a critical node in a brain network that controls sleep onset and homeostasis. By contrast, we recently reported that a group of glutamatergic neurons in the lateral and medial preoptic area increases wakefulness, challenging the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic. However, the precise role of these subcortical neurons in the control of behavioral state transitions and cortical dynamics remains unknown. Therefore, in this study we used conditional expression of excitatory hM3Dq receptors in these preoptic glutamatergic (Vglut2+) neurons and show that their activation initiates wakefulness, decreases non-rapid eye movement (NREM) sleep, and causes a persistent suppression of rapid eye movement (REM) sleep. Activation of preoptic glutamatergic neurons also causes a high degree of NREM sleep fragmentation, promotes state instability with frequent arousals from sleep, and shifts cortical dynamics (including oscillations, connectivity, and complexity) to a more wake-like state. We conclude that a subset of preoptic glutamatergic neurons may initiate -but not maintain- arousals from sleep, and their inactivation may be required for NREM stability and REM sleep generation. Further, these data provide novel empirical evidence supporting the conclusion that the preoptic area causally contributes to the regulation of both sleep and wakefulness.

neuroscience↗

bioRxiv2020

Power and coherence in the EEG of the rat: impact of behavioral states, cortical area, lateralization and light/dark phases

The sleep-wake cycle is constituted by three behavioral states: wakefulness (W), non-REM (NREM) and REM sleep. These states are associated with drastic changes in cognitive capacities, mostly determined by the function of the thalamo-cortical system. Thalamo-cortical activity can be examined by means of the intra-cranial electroencephalogram (iEEG). With the purpose to study in depth the basal activity of the iEEG in adult rats, we analyzed the spectral power and coherence of the iEEG during W and sleep in the paleocortex (olfactory bulb), as well as in motor, somatosensory and visual neocortical areas. We also analyzed the laterality (right Vs. left hemispheres) of the signals, as well as the iEEG in function of the light and dark phases. We found that the iEEG power and coherence of the whole spectrum were largely affected by behavioral states and were highly dependent on the cortical areas recorded. We also determined that there are night/day differences in power and coherence during sleep, but not in W. Finally, while we did not find right/left differences in power either in W or sleep, we observed that during REM sleep intra-hemispheric coherence differs between both hemispheres. We conclude that the iEEG dynamics is highly dependent on the cortical area and behavioral states. We also determine that there are light/dark phases disparities in the iEEG that emerge during sleep, and that intra-hemispheric connectivity differs between both hemispheres only during REM sleep.

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bioRxiv2020

Gamma band alterations and REM-like traits underpin the acute effect of the atypical psychedelic ibogaine

Ibogaine is a psychedelic alkaloid that has attracted scientific interest because of its important antiaddictive properties evidenced in observational studies in humans, and in models for substance-use-disorders in rodents. Its subjective effect has been described as intense vivid dream-like experiences occurring while awake; hence, ibogaine is often referred to as an oneirogenic psychedelic. While this unique dream-like profile has been hypothesized to aid the antiaddictive effects in the past, the electrophysiological signatures of the ibogaine psychedelic state remain unknown. In our previous work, we showed in rats that ibogaine administration promotes a waking state with abnormal motor behavior, accompanied by a decrease in NREM and REM sleep. Here, we performed an in-depth analysis of the intracranial electroencephalogram during "ibogaine wakefulness". Ibogaine induced gamma oscillations with larger power than control levels but less coherent and less complex; i.e., this state shows clear REM sleep traits within the gamma frequency band. Thus, our results provide novel biological evidence for the association between the psychedelic state and REM sleep, and an empirical basis for the oneirogenic conjecture of ibogaine.

neuroscience↗

bioRxiv2020

Communication through coherence by means of cross-frequency coupling

The theory of communication through coherence (CTC) posits the synchronization of brain oscillations as a key mechanism for information sharing and perceptual binding. In a parallel literature, hippocampal theta activity (4 - 10 Hz) has been shown to modulate the appearance of neocortical fast gamma oscillations (100 - 150 Hz), a phenomenon known as cross-frequency coupling (CFC). Even though CFC has also been previously associated with information routing, it remains to be determined whether it directly relates to CTC. In particular, for the theta-fast gamma example at hand, a critical question is to know if the phase of the theta cycle influences gamma synchronization across the neocortex. To answer this question, we designed a new screening method for detecting the modulation of the cross-regional high-frequency synchronization by the phase of slower oscillations. Upon applying the method, we found that the long-distance synchronization of neocortical fast gamma during REM sleep depends on the instantaneous phase of the theta rhythm. These results show that CFC is likely to aid long-range information transfer by facilitating the cross-regional synchronization of faster rhythms, thus consistent with classical CTC views.

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bioRxiv2020

Electrocortical temporal complexity during wakefulness and sleep: an updated account

The states of sleep and wakefulness are critical physiological processes associated with different brain patterns of activity. The intracranial electroencephalogram allows us to measure these changes, thus, it is a critical tool for its study. Recently, we showed that the electrocortical temporal complexity decreased from wakefulness to sleep. Nevertheless, the origin of this complex activity remains a controversial topic due to the existence of possible artifacts contaminating the brain signals. In this work, we showed that complexity decreases during sleep, independently of the electrode configuration employed. This fact strongly suggests that the basis for the behavioral-state differences in complexity does not have an extracranial origin; i.e., generated from the brain.

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bioRxiv2018

Nasal respiration entrains neocortical long-range gamma coherence during wakefulness

Recent studies have shown that slow cortical potentials in archi-, paleo- and neocortex, can phase-lock with nasal respiration. In some of these areas, gamma activity ({gamma}: 30-100 Hz) is also coupled to the animals respiration. It has been hypothesized that this interaction plays a role in coordinating distributed neural activity. In a similar way, inter-cortical interactions at {gamma} frequency has been also associated as a binding mechanism by which the brain generates temporary opportunities necessary for implementing cognitive functions. The aim of the present study is to explore if nasal respiration entrains inter-cortical interactions at {gamma} frequency.\n\nSix adult cats chronically prepared for electrographic recordings were employed in this study. Our results show that slow cortical respiratory potentials are present in several areas of the neocortex and olfactory bulb during wakefulness. Also, we found cross-frequency coupling between the respiratory phase and the amplitude of {gamma} activity in all recorded areas. These oscillatory entrainments are independent of muscular activity, because are maintained during cataplexy induced by carbachol microinjection into the nucleus pontis oralis. Importantly, we observed that respiratory phase modulates the inter-cortical gamma coherence between neocortical pairs of electrodes during wakefulness. However, during NREM and REM sleep, breathing was unable to entrain the oscillatory activity, neither in the olfactory bulb nor in the neocortex. These results suggest a single unified phenomenon involving cross frequency coupling and long-range {gamma} coherence across the neocortex. This fact could be related to a temporal binding process necessary for cognitive functions during wakefulness.

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