Respiration and rapid eye movement (REM) sleep substructure: short versus long episodes.

Rapid eye movement (REM) sleep in rodents is defined by the presence of theta rhythm in the absence of movement. The amplitude and frequency of theta oscillations have been used to distinguish between tonic and phasic REM sleep. However, tonic REM sleep has not been further subdivided, although characteristics of network oscillations such as cross-frequency coupling between theta and gamma vary within this sub-state.

Breathing modulates gamma synchronization across species.

Nasal respiration influences brain dynamics by phase-entraining neural oscillations at the same frequency as the breathing rate and by phase-modulating the activity of faster gamma rhythms. Despite being widely reported, we still do not understand the functional roles of respiration-entrained oscillations. A common hypothesis is that these rhythms aid long-range communication and provide a privileged window for synchronization.

Respiratory entrainment of units in the mouse parietal cortex depends on vigilance state.

Synchronous oscillations are essential for coordinated activity in neuronal networks and, hence, for behavior and cognition. While most network oscillations are generated within the central nervous system, recent evidence shows that rhythmic body processes strongly influence activity patterns throughout the brain. A major factor is respiration (Resp), which entrains multiple brain regions at the mesoscopic (local field potential) and single-cell levels.

Differential modulation of parietal cortex activity by respiration and θ oscillations.

The simultaneous, local integration of information from widespread brain regions is an essential feature of cortical computation and particularly relevant for multimodal association areas such as the posterior parietal cortex. Slow, rhythmic fluctuations in the local field potentials (LFPs) are assumed to constitute a global signal aiding interregional communication through the long-range synchronization of neuronal activity. Recent work demonstrated the brain-wide presence of a novel class of slow neuronal oscillations that are entrained by nasal respiration.

Theta-gamma coupling during REM sleep depends on breathing rate.

Temporal coupling between theta and gamma oscillations is a hallmark activity pattern of several cortical networks and becomes especially prominent during REM sleep. In a parallel approach, nasal breathing has been recently shown to generate phase-entrained network oscillations which also modulate gamma. Both slow rhythms (theta and respiration-entrained oscillations) have been suggested to aid large-scale integration but they differ in frequency, display low coherence, and modulate different gamma sub-bands.

Temporal Relations between Cortical Network Oscillations and Breathing Frequency during REM Sleep.

Nasal breathing generates a rhythmic signal which entrains cortical network oscillations in widespread brain regions on a cycle-to-cycle time scale. It is unknown, however, how respiration and neuronal network activity interact on a larger time scale: are breathing frequency and typical neuronal oscillation patterns correlated? Is there any directionality or temporal relationship? To address these questions, we recorded field potentials from the posterior parietal cortex of mice together with respiration during REM sleep. In this state, the parietal cortex exhibits prominent θ and γ oscillations while behavioral activity is minimal, reducing confounding signals.

A New Apparatus for Recording Evoked Responses to Painful and Non-painful Sensory Stimulation in Freely Moving Mice.

Experiments on pain processing in animals face several methodological challenges including the reproducible application of painful stimuli. Ideally, behavioral and physiological correlates of pain should be assessed in freely behaving mice, avoiding stress, fear or behavioral restriction as confounding factors. Moreover, the time of pain-evoked brain activity should be precisely related to the time of stimulation, such that pain-specific neuronal activity can be unambiguously identified.

Alterations of distributed neuronal network oscillations during acute pain in freely-moving mice.

The experience of pain involves the activation of multiple brain areas. Pain-specific activity patterns within and between these local networks remain, however, largely unknown. We measured neuronal network oscillations in different relevant regions of the mouse brain during acute pain, induced by subcutaneous injection of capsaicin into the left hind paw.

Parallel detection of theta and respiration-coupled oscillations throughout the mouse brain.

Slow brain oscillations are usually coherent over long distances and thought to link distributed cell assemblies. In mice, theta (5-10 Hz) stands as one of the most studied slow rhythms. However, mice often breathe at theta frequency, and we recently reported that nasal respiration leads to local field potential (LFP) oscillations that are independent of theta.

Respiration-Entrained Brain Rhythms Are Global but Often Overlooked.

We revisit recent evidence showing that nasal respiration entrains oscillations at the same frequency as breathing in several regions of the rodent brain. Moreover, respiration modulates the amplitude of a specific gamma sub-band (70-120Hz), most prominently in frontal regions. Since rodents often breathe at delta and theta frequencies, we caution that previous studies on delta and theta power and their cross-regional synchrony, as well as on delta-gamma and theta-gamma coupling, may have detected the respiration-entrained rhythm and respiration-gamma coupling.

Selective entrainment of gamma subbands by different slow network oscillations.

Theta oscillations (4-12 Hz) are thought to provide a common temporal reference for the exchange of information among distant brain networks. On the other hand, faster gamma-frequency oscillations (30-160 Hz) nested within theta cycles are believed to underlie local information processing. Whether oscillatory coupling between global and local oscillations, as showcased by theta-gamma coupling, is a general coding mechanism remains unknown.

Olfactory Bulb Field Potentials and Respiration in Sleep-Wake States of Mice.

It is well established that local field potentials (LFP) in the rodent olfactory bulb (OB) follow respiration. This respiration-related rhythm (RR) in OB depends on nasal air flow, indicating that it is conveyed by sensory inputs from the nasal epithelium. Recently RR was found outside the olfactory system, suggesting that it plays a role in organizing distributed network activity.

Impaired theta-gamma coupling in APP-deficient mice.

Amyloid precursor protein (APP) is critically involved in the pathophysiology of Alzheimer's disease, but its physiological functions remain elusive. Importantly, APP knockout (APP-KO) mice exhibit cognitive deficits, suggesting that APP plays a role at the neuronal network level. To investigate this possibility, we recorded local field potentials (LFPs) from the posterior parietal cortex, dorsal hippocampus and lateral prefrontal cortex of freely moving APP-KO mice.

Hippocampal Respiration-Driven Rhythm Distinct from Theta Oscillations in Awake Mice.

Unlabelled: We have recently described a slow oscillation in the hippocampus of urethane-anesthetized mice, which couples to nasal respiration and is clearly distinct from co-occurring theta oscillations. Here we set out to investigate whether such type of patterned network activity, which we named "hippocampal respiration rhythm" (HRR), also occurs in awake mice. In freely moving mice, instantaneous respiration rate is extremely variable, and respiration is superimposed by bouts of sniffing.

Slow oscillations in the mouse hippocampus entrained by nasal respiration.

Different types of network oscillations occur in different behavioral, cognitive, or vigilance states. The rodent hippocampus expresses prominent θ oscillations at frequencies between 4 and 12 Hz, which are superimposed by phase-coupled γ oscillations (30-100 Hz). These patterns entrain multineuronal activity over large distances and have been implicated in sensory information processing and memory formation.

Global slowing of network oscillations in mouse neocortex by diazepam.

Benzodiazepines have a broad spectrum of clinical applications including sedation, anti-anxiety, and anticonvulsive therapy. At the cellular level, benzodiazepines are allosteric modulators of GABA(A) receptors; they increase the efficacy of inhibition in neuronal networks by prolonging the duration of inhibitory postsynaptic potentials. This mechanism of action predicts that benzodiazepines reduce the frequency of inhibition-driven network oscillations, consistent with observations from human and animal EEG.

Theta-associated high-frequency oscillations (110-160Hz) in the hippocampus and neocortex.

We review recent evidence for a novel type of fast cortical oscillatory activity that occurs circumscribed between 110 and 160Hz, which we refer to as high-frequency oscillations (HFOs). HFOs characteristically occur modulated by theta phase in the hippocampus and neocortex. HFOs can co-occur with gamma oscillations nested in the same theta cycle, in which case they typically peak at different theta phases.

Distinct features of fast oscillations in phasic and tonic rapid eye movement sleep.

Spatiotemporal activity patterns of neurones are organized by different types of coherent network oscillations. Frequency content and cross-frequency coupling of cortical oscillations are strongly state-dependent, indicating that different patterns of wakefulness or sleep, respectively, support different cognitive or mnestic processes. It is therefore crucial to analyse specific sleep patterns with respect to their oscillations, including interaction between fast and slow rhythms.

Selective coupling between theta phase and neocortical fast gamma oscillations during REM-sleep in mice.

Background: The mammalian brain expresses a wide range of state-dependent network oscillations which vary in frequency and spatial extension. Such rhythms can entrain multiple neurons into coherent patterns of activity, consistent with a role in behaviour, cognition and memory formation. Recent evidence suggests that locally generated fast network oscillations can be systematically aligned to long-range slow oscillations.

EEG gamma frequency and sleep-wake scoring in mice: comparing two types of supervised classifiers.

There is growing interest in sleep research and increasing demand for screening of circadian rhythms in genetically modified animals. This requires reliable sleep stage scoring programs. Present solutions suffer, however, from the lack of flexible adaptation to experimental conditions and unreliable selection of stage-discriminating variables.

Sleep and hippocampus: do we search for the right things?

In addition to its established function in brain restoration, energy saving, circadian homeostasis, thermoregulation, and ontogenetic brain development, sleep is involved in replay and restructuring of memory representations that may lead to memory consolidation. The degree of availability of these memory-related functions in various species, and in disparate environmental and behavioral situations is widely debated. Generally it seems that species which can afford to sleep deeply show an involvement of sleep in learning and memory, both, hippocampus-dependent and hippocampus-independent.

Entorhinal inputs to dentate gyrus are activated mainly by conditioned events with long time intervals.

Brain mechanisms of mammalian learning and memory have long been associated with the hippocampus. Although the role of the hippocampus in spatial behavior is well established, there is no general consensus on the function of the hippocampus in nonspatial tasks. Task-related changes in evoked potentials were first reported by Deadwyler and colleagues in the dentate gyrus, with a peak at 100 ms in rats trained in an auditory discrimination task (Deadwyler et al.