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Cavelli, M. L.

Publications and source records attributed to Cavelli, M. L..

5 recordsLinked to original sources

Early Sleep-Dependent Sensory Gating in the Olfactory System

Disconnection from the external world is a defining feature of sleep. Although most models attribute sensory gating to thalamocortical mechanisms, the olfactory system--bypassing the thalamus--offers a unique window into earlier stages of sensory disconnection. Here, we combine chronic and acute recordings in rodents to test whether nasal sensory inputs are internalized during sleep. We show that respiration-locked potentials and gamma activity in the olfactory bulb are strongly modulated by brain state: they diminish during sleep and reappear during wakefulness and cortical activation. This gating occurs independently of respiratory dynamics and arises near the first synapse of the olfactory pathway. Finally, we find that neocortical slow-wave activity correlates with reduced connectiveness, with coupling progressively vanishing as sleep deepens. These findings reveal a sleep-dependent sensory gating mechanism at early stages of a non-thalamic pathway, providing new insights into the neural substrates of sensory disconnection during sleep.

neuroscience↗

Behavioral and cortical arousal from sleep, muscimol-induced coma, and anesthesia by direct optogenetic stimulation of cortical neurons

The cerebral cortex is widely considered part of the neural substrate of consciousness. However, while several studies have demonstrated that stimulation of subcortical nuclei can produce EEG activation and restore consciousness, so far no direct causal evidence has been available for the cortex itself. Here we tested in mice whether optogenetic activation of cortical neurons in posterior parietal cortex (PtA) or medial prefrontal cortex (mPFC) is sufficient for arousal from three behavioral states characterized by progressively deeper unresponsiveness: sleep, a coma-like state induced by muscimol injection in the midbrain, and deep sevoflurane-dexmedetomidine anesthesia. We find that cortical stimulation always awakens the mice from both NREM sleep and REM sleep, with PtA requiring weaker/shorter light pulses than mPFC. Moreover, in most cases light pulses produce both cortical activation (decrease in low frequencies) and behavioral arousal (recovery of the righting reflex) from brainstem coma, as well as cortical activation from anesthesia. These findings provide evidence that direct activation of cortical neurons is sufficient for behavioral and/or cortical arousal from sleep, brainstem coma, and anesthesia.

neuroscience↗

Cortical high-frequency oscillations ({approx} 110 Hz) in cats are state-dependent and enhanced by a subanesthetic dose of ketamine

Ketamine is an NMDA receptor antagonist that has both antidepressant and anesthetic properties. At subanesthetic doses, ketamine can cause transient psychosis in humans, and is used to model psychosis in experimental animals. In rodents, subanesthetic doses of ketamine increase the power of high-frequency oscillations (HFO, 100-180 Hz) in the electroencephalogram and field potentials, a frequency band linked to cognitive functions. However, the effects of ketamine in higher mammals, with more translatable relevance, are poorly investigated. Here, we have examined cortical HFO during wakefulness, sleep, and after administering a sub-anesthetic dose of ketamine (15 mg/kg), utilizing the cat as an animal model. Four cats were implanted with cortical electrodes for chronic polysomnographic recordings. HFO power, connectivity, information flow directionality, and their relationships with respiratory activity were analyzed. During wakefulness, but not during sleep, we found that HFO were coupled with the inspiratory phase of the respiration. After ketamine administration, HFO were enhanced significantly and remained associated with the inspiratory phase. The analysis of the information flow after ketamine suggest that HFO originate from the olfactory bulb and stream towards the prefrontal cortex. Accordingly, occluding the nostrils significantly reduced HFO power in both the olfactory bulb and prefrontal cortex. In contrast, auditory stimulation did not affect HFO. In conclusion, spontaneous cortical HFO show certain state-dependent features in cats, and enhancement of this rhythm by ketamine may disrupt cortical information processing, which could contribute to some of the neuropsychiatric manifestations associated with ketamine. HighlightsO_LIKetamine is used to model psychosis in humans and experimental animals C_LIO_LISubanesthetic doses of ketamine increase the power of high-frequency oscillations C_LIO_LIHigh-frequency oscillations are coupled with the inspiratory phase of respiration C_LIO_LIThese oscillations originate in the olfactory bulb and stream to the neocortex C_LIO_LINostril occlusion lowers high-frequency activity in the olfactory bulb and neocortex C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/543142v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@e386feorg.highwire.dtl.DTLVardef@1b3c06aorg.highwire.dtl.DTLVardef@1d93ecorg.highwire.dtl.DTLVardef@1daa161_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Sleep/wake changes in perturbational complexity in rats and mice

In humans, the level of consciousness can be assessed by quantifying the spatiotemporal complexity of cortical responses using the Perturbational Complexity Index (PCI) and related PCIst (st, state transitions). These measures are consistently high in wake and rapid eye movement (REM) sleep and low in dreamless non-REM (NREM) sleep, deep slow wave anesthesia, and coma. The neuronal mechanisms underlying the reduction of PCI/PCIst in unconscious states remain largely unexplored. The extent to which different cortical areas or layers contribute to these measures is also unknown. To address these questions, here we first validate the use of PCIst in freely moving rats (8 males) and mice (12, 4 females) by showing that its values are lower in NREM sleep and slow wave anesthesia than in wake or REM sleep, as in humans. We then show that low PCIst is associated with the occurrence of an OFF period of neuronal silence. Moreover, the stimulation of deep, but not superficial, cortical layers leads to reliable changes in PCIst across sleep/wake and anesthesia. Finally, consistent changes in PCIst can be measured independent of which single area is being stimulated or recorded, except for recordings in mouse prefrontal cortex. These experiments directly support the hypothesis that PCIst is low when an OFF period disrupts causal interactions in cortical networks. Moreover, they demonstrate that, as in humans, PCIst can be used for the reliable assessment of vigilance states in unresponsive animals, without the need to rely on behavioral outputs such as the righting reflex. Significance StatementThe level of consciousness can be assessed in humans by measuring the spatiotemporal complexity of cortical responses using the Perturbational Complexity Index (PCI) and related PCIst. These measures discriminate between conscious and unconscious conditions with high sensitivity and specificity and work in unresponsive patients. However, the neuronal mechanisms underlying PCI/ PCIst are largely unexplored. Moreover, since they reflect evoked responses from many cortical regions, it is unclear whether some areas or layers are more informative than others. Here we validate PCIst in rodents, provide direct evidence for the underlying neuronal mechanisms, and show that reliable changes in PCIst can almost always be obtained independent of which single area is stimulated or recorded, but only after stimulation of deep layers.

neuroscience↗

Decreased electrocortical temporal complexity distinguishes sleep from wakefulness

In most mammals, the sleep-wake cycle is constituted by three behavioral states: wakefulness (W), non-NREM (NREM) sleep, and REM sleep. These states are associated with drastic changes in cognitive capacities, mostly determined by the function of the thalamo-cortical system. The intra-cranial electroencephalogram or electocorticogram (ECoG), is an important tool for measuring the changes in the thalamo-cortical activity during W and sleep. In the present study we analyzed broad-band ECoG recordings of the rat by means of a time-series complexity measure that is easy to implement and robust to noise: the Permutation Entropy (PeEn). We found that PeEn is maximal during W and decreases during sleep. These results bring to light the different thalamo-cortical dynamics emerging during sleep-wake states, which are associated with the well-known spectral changes that occur when passing from W to sleep. Moreover, the PeEn analysis allows to determine behavioral states independently of the electrodes cortical location, which points to an underlying global pattern in the signal that differs among the cycle states that is missed by classical methods. Consequently, our data suggest that PeEn analysis of a single EEG channel could allow for cheap, easy, and efficient sleep monitoring.

neuroscience↗