Impaired electrical signaling disrupts gamma frequency oscillations in connexin 36-deficient mice

Neural processing occurs in parallel in distant cortical areas even for simple perceptual tasks. Associated cognitive binding is believed to occur through the interareal synchronization of rhythmic activity in the gamma (30-80 Hz) range. Such oscillations arise as an emergent property of the neuronal network and require conventional chemical neurotransmission. To test the potential role of gap junction-mediated electrical signaling in this network property, we generated mice lacking connexin 36, the major neuronal connexin. Here we show that the loss of this protein disrupts gamma frequency network oscillations in vitro but leaves high frequency (150 Hz) rhythms, which may involve gap junctions between principal cells (Schmitz et al., 2001), unaffected. Thus, specific connexins differentially deployed throughout cortical networks are likely to regulate different functional aspects of neuronal information processing in the mature brain.     

COMPARISON OF OSCILLATIONS OF SKIN BLOOD FLOW AND DEOXYGENATION IN VASTUS LATERALIS IN LIGHT EXERCISE

The purpose of the present study was to compare oscillation of skin blood flow with that of deoxygenation in muscle during light exercise in order to determine the physiological significance of oscillations in deoxygenation. Prolonged exercise with 50% of peak oxygen uptake was performed for 60 min. Skin blood flow (SBF) was measured using a laser blood flow meter on the right vastus lateralis muscle. Deoxygenated haemoglobin/myoglobin (DHb/Mb) concentration in the left vastus lateralis were measured using a near-infrared spectroscopy system. SBF and DHb/Mb during exercise were analysed by fast Fourier transform. We classified frequency bands according to previous studies (Kvernmo et al. 1999, Kvandal et al. 2006) into phase I (0.005-0.0095 and 0.0095-0.02 Hz), phase II (0.02-0.06 Hz: phase II) and phase III (0.06-0.16 Hz). The first peak of power spectra density (PSD) in SBF appeared at 0.0078 Hz in phase I. The second peak of PSD in SBF appeared at 0.035 Hz. The third peak of PSD in SBF appeared at 0.078 Hz. The first peak of PSD in DHb/Mb appeared at 0.0039 Hz, which was out of phase I. The second peak of PSD in DHb/Mb appeared at 0.016 Hz. The third peak of PSD in DHb/Mb appeared at 0.035 Hz. The coefficient of cross correlation was very low. Cross power spectra density showed peaks of 0.0039, 0.016 and 0.035 Hz. It is concluded that a peak of 0.016 Hz in oscillations of DHb/Mb observed in muscle during exercise is associated with endothelium-dependent vasodilation (phase I) and that a peak of 0.035 Hz in DHb/Mb is associated with sympathetic nerve activity (phase II). It is also confirmed that each peak of SBF oscillations is observed in each phase.     

Paving the way forward: integrating the senses through phase-resetting of cortical oscillations

Most, if not all, of the neocortex is multisensory, but the mechanisms by which different cortical areas - association versus sensory, for instance - integrate multisensory inputs are not known. The study by Lakatos et al. reveals that, in the primary auditory cortex, the phase of neural oscillations is reset by somatosensory inputs, and subsequent auditory inputs are enhanced or suppressed, depending on their timing relative to the oscillatory cycle.     

Mechanisms underlying gamma ('40 Hz') network oscillations in the hippocampus--a mini-review

Gamma-frequency oscillations (approximately 30-100 Hz) in cortical network activity have been proposed to provide a temporal structure for various forms of cognitive processing. This review provides an update on recent experiments addressing the mechanisms underlying gamma-frequency network oscillations in the rodent hippocampus. Particular emphasis is placed on the correlation between in vivo observations and in vitro models.     

A new look at gamma? High- (>60 Hz) γ-band activity in cortical networks: function, mechanisms and impairment

γ-band oscillations are thought to play a crucial role in information processing in cortical networks. In addition to oscillatory activity between 30 and 60 Hz, current evidence from electro- and magnetoencephalography (EEG/MEG) and local-field potentials (LFPs) has consistently shown oscillations >60 Hz (high γ-band) whose function and generating mechanisms are unclear. In the present paper, we summarize data that highlights the importance of high γ-band activity for cortical computations through establishing correlations between the modulation of oscillations in the 60-200 Hz frequency and specific cognitive functions. Moreover, we will suggest that high γ-band activity is impaired in neuropsychiatric disorders, such as schizophrenia and epilepsy. In the final part of the paper, we will review physiological mechanisms underlying the generation of high γ-band oscillations and discuss the functional implications of low vs. high γ-band activity patterns in cortical networks.     

Ionic and osmotic disruptions of the lily pollen tube oscillator: testing proposed models

Two mechanisms have been proposed as the primary control of oscillating tip growth in Lilium longiflorum Thunb. pollen tubes: changes in cell wall strength (Holdaway-Clarke et al. 1997) or alternatively, changes in turgor pressure (Messerli et al. 2000). Here we have modified the ionic and osmotic concentrations of the growth medium to test predictions derived from both models. Raising the [Ca2+]o tenfold above normal reduced the amplitude of the [Ca2+]i oscillations and growth oscillations while it raised the basal [Ca2+]i and growth rate such that the average growth rate did not change. Raising the [H+] of the growth medium tenfold reversibly decreased and sometimes eliminated the [Ca2+]i and growth oscillations without changing the average growth rate. Lowering the [H+] tenfold led to irregular frequency and amplitude [Ca2+]i oscillations, reduced the average growth rate of tubes and led to cell bursting in 33% of tubes. Addition of 50 mM H+ buffer, MES, to prevent pH changes in the cell wall increased the period, amplitude and duration of both [Ca2+]i and growth oscillations. Changing the [K+]o did not markedly effect [Ca2+]i oscillations. Reducing the osmolarity of the medium led to transient large-amplitude [Ca2+]i and growth oscillations while reducing large-amplitude oscillations over long periods. In many different conditions under which growth still occurs, lily pollen tubes maintain growth oscillations, albeit with modified frequency, amplitude and duration. We conclude that modifications to both proposed models are necessary to explain oscillating growth in this system.     

The segmentation clock in mice: interaction between the Wnt and Notch signalling pathways

In the last few years, the efforts to elucidate the mechanisms underlying the segmentation clock in various vertebrate species have multiplied. Early evidence suggested that oscillations are caused by one of the genes under the Notch signalling pathway (like those of the her or Hes families). Recently, Aulehla et al. [Wnt3a plays a major role in the segmentation clock controlling somitogenesis. Dev. Cell 4, 395-406] discovered that Axin2 (a gene under the Wnt3a signalling pathway) also oscillates in the presomitic mesoderm (PSM) of mice embryos and proposed some mechanisms through which the Notch and Wnt3a pathways may interact. They further suggested that a decreasing concentration of Wnt3a along the PSM may be the gradient the segmentation clock interacts with to form somites. These results were reviewed by Rida et al. [A notch feeling of somite segmentation and beyond. Dev. Biol. 265, 2-22], who introduced a complex clockwork comprising genes Hes1, Lfng (under the Notch pathway), and Axin2, as well as their multiple interactions. In the present work we develop a mathematical model based on the Rida et al. review and use it to tackle some of the questions raided by the Aulehla et al. paper: can the Axin2 feedback loop constitute a clock? Could a decreasing Wnt3a signaling constitute the wavefront, where phase is recorded and the spatial pattern laid down? What is the master oscillator?     

Preferential axial flow during high-frequency oscillations: effects of gas density

Allen et al. (J. Clin. Invest. 76: 620-629, 1985) reported that regional phasic lung distension during high-frequency oscillations (HFO) is substantially and systemically heterogeneous when both frequency (f) and tidal volume (VT) are large. They hypothesized that this phenomenon was attributable to central airway geometry and preferential axial flow induced therein by the momentum flux of the inspiratory gas stream. According to that hypothesis, the observed distribution of phasic lung distension would depend on the ratio VT/VD* (where VD* is an index of anatomic dead space), independent of gas density (rho), when f is scaled in proportion to lung resonant frequency, fo. To test this hypothesis, we used the methods of Allen et al. (ibid.) to study six excised dog lungs during HFO (f = 2-32 Hz; VT = 5-80 ml) using gases of different densities. Alveolar pressure excursions (PA) were measured as rho spanned a 12-fold range using He, air, and SF6. The apex-to-base and right-to-left ratios of PA were used as indexes of regional heterogeneity of phasic lung distension. For each gas at low f, distension of the lung base was favored slightly independent of VT, but at higher f distension of the lung apex was favored when VT was small, whereas distension of the lung base was favored when VT was large. In addition, we observed substantial right-to-left differences in apical lobes during oscillation at high f not seen before.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rhythmic cortical neurons increase their oscillations and sculpt basal ganglia signaling during motor learning

The function and modulation of neural circuits underlying motor skill may involve rhythmic oscillations (Feller, 1999 ; Marder and Goaillard, 2006 ; Churchland et al., 2012 ). In the proposed pattern generator for birdsong, the cortical nucleus HVC, the frequency and power of oscillatory bursting during singing increases with development (Crandall et al., 2007 ; Day et al., 2009 ). We examined the maturation of cellular activity patterns that underlie these changes. Single unit ensemble recording combined with antidromic identification (Day et al., 2011 ) was used to study network development in anesthetized zebra finches. Autocovariance quantified oscillations within single units. A subset of neurons oscillated in the theta/alpha/mu/beta range (8–20 Hz), with greater power in adults compared to juveniles. Across the network, the normalized oscillatory power in the 8–20 Hz range was greater in adults than juveniles. In addition, the correlated activity between rhythmic neuron pairs increased with development. We next examined the functional impact of the oscillators on the output neurons of HVC. We found that the firing of oscillatory neurons negatively correlated with the activity of cortico‐basal ganglia neurons (HVC_Xs), which project to Area X (the song basal ganglia). If groups of oscillators work together to tonically inhibit and precisely control the spike timing of adult HVC_Xs with coordinated release from inhibition, then the activity of HVC_Xs in juveniles should be decreased relative to adults due to uncorrelated, tonic inhibition. Consistent with this hypothesis, HVC_Xs had lower activity in juveniles. These data reveal network changes that shape cortical‐to‐basal ganglia signaling during motor learning. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 754–768, 2013     

Oscillations in a Simple Neuromechanical System: Underlying Mechanisms

A half-center neural oscillator was coupled to a simple mechanical system to study the closed-loop interactions between a central pattern generator and its effector muscles. After a review of the open-loop mechanisms that were previously introduced by Skinner et al. (1994), we extend their geometric approach and introduce four additional closed-loop mechanisms by the inclusion of an antagonistic muscle pair acting on a mass and connected to the half-center neural oscillator ipsilaterally. Two of the closed-loop mechanisms, mechanical release mechanisms, have close resemblance to open-loop release mechanisms whereas the latter two, afferent mechanisms, have a strong dependence on the mechanical properties of the system. The results also show that stable oscillations can emerge in the presence of sensory feedback even if the neural system is not oscillatory. Finally, the feasibility of the closed-loop mechanisms was shown by weakening the idealized assumptions of the synaptic and the feedback connections as well as the rapidity of the oscillations.     

Coupling between Intrinsic Prefrontal HbO2 and Central EEG Beta Power Oscillations in the Resting Brain

There is increasing interest in the intrinsic activity in the resting brain, especially that of ultraslow and slow oscillations. Using near-infrared spectroscopy (NIRS), electroencephalography (EEG), blood pressure (BP), respiration and heart rate recordings during 5 minutes of rest, combined with cross spectral and sliding cross correlation calculations, we identified a short-lasting coupling (duration [Formula: see text] s) between prefrontal oxyhemoglobin (HbO2) in the frequency band between 0.07 and 0.13 Hz and central EEG alpha and/or beta power oscillations in 8 of the 9 subjects investigated. The HbO2 peaks preceded the EEG band power peaks by 3.7 s in 6 subjects, with moderate or no coupling between BP and HbO2 oscillations. HbO2 and EEG band power oscillations were approximately in phase with BP oscillations in the 2 subjects with an extremely high coupling (squared coherence [Formula: see text]) between BP and HbO2 oscillation. No coupling was identified in one subject. These results indicate that slow precentral (de)oxyhemoglobin concentration oscillations during awake rest can be temporarily coupled with EEG fluctuations in sensorimotor areas and modulate the excitability level in the brains' motor areas, respectively. Therefore, this provides support for the idea that resting state networks fluctuate with frequencies of between 0.01 and 0.1 Hz (Mantini et.al. PNAS 2007).     

Effects of temperature on the subjective magnitude of vibration

Absolute magnitude estimation (AME) was used to determine the effects of skin temperature on the subjective magnitude of vibration delivered to the thenar eminence of the right hand. Measurements were made at three frequencies chosen to selectively activate cutaneous mechanoreceptor channels, namely NP I and NP III (Meissner and Merkel cell-neurite receptors, respectively) at 15 Hz, Pacinian (250 Hz, 400 Hz) and NP III (Ruffini endings) at 400 Hz. Skin temperatures at 15, 20 and 40 degrees C were tested at 11 suprathreshold displacement levels. It was concluded that the subjective magnitude of vibration is influenced by temperature in the Pacinian channel, but in the NP I and NP III channels the temperature of the skin did not have an effect upon judgements of subjective magnitude. This is consistent with earlier work by Verrillo and Bolanowski (J Acoust Soc Am 80: 528-532, 1986) and Bolanowski et al. (J Acoust Soc Am 84: 1680-1694, 1988); both studies show only modest effects of temperature at threshold at frequencies below approximately 40 Hz.     

Measurement of total respiratory impedance in infants by the forced oscillation technique

The forced oscillation technique according to Làndsér et al. (J. Appl. Physiol. 41:101-106, 1976) was modified for use in infants. Adaptations, including a flexible tube to connect the infant to the measuring system and a bias flow to avoid rebreathing, did not influence impedance values. The linearity of the respiratory system was assessed and confirmed by 1) applying pseudo-random noise oscillations at three different amplitudes to 7 infants and 2) comparing in 12 infants impedance values obtained with pseudo-random noise and with sinusoidal oscillations at 12 and 32 Hz. Intersubject variability, averaged for all frequencies, was 6%. In 17 infants the relative error (+/- SD) between two series of five measurements within a time interval of 15 min was 0.5 +/- 5.7%. No statistically significant difference was found between impedance values before and after repositioning of the infant's head, whereas rotation resulted in a decrease in resistance and no effect on reactance. Our results indicate that the infant-adapted forced pseudo-random noise oscillation technique has the potential to give valuable information about ventilatory lung function in infants.     

Somatic evoked high-frequency magnetic oscillations reflect activity of inhibitory interneurons in the human somatosensory cortex

High-frequency potential oscillations in the range of 300–900 Hz have recently been shown to concur with the primary response (N20) of the somatosensory cortex in awake humans. However, the physiological mechanisms of the high-frequency oscillations remained undetermined. We addressed the issue by analyzing magnetic fields during wakefulness and sleep over the left hemisphere to right median nerve stimulation with a wide bandpass (0.1–2000 Hz) recording with subsequent high-pass (> 300 Hz) and low-pass (< 300 Hz) filtering. With wide bandpass recordings, high-frequency magnetic oscillations with the main signal energy at 580–780 Hz were superimposed on the N20m during wakefulness. Isofield mapping at each peak of the high-pass filtered and isolated high-frequency oscillations showed a dipolar pattern and the estimated source for these peaks was the primary somatosensory cortex (area 3b) very close to that for the N20m peak. During sleep, the high-frequency oscillations showed dramatic diminution in amplitude while the N20m amplitude exhibited a moderate increment. This reciprocal relation between the high-frequency oscillations and the N20m during a wake-sleep cycle suggests that they represent different generator substrates. We speculate that the high-frequency oscillations represent a localized activity of the GABAergic inhibitory interneurons of layer 4, which have been shown in animal experiments to respond monosynaptically to thalamo-cortical input with a high-frequency (600–900 Hz) burst of short duration spikes. On the other hand, the underlying N20m represents activity of pyramidal neurons which receive monosynaptic excitatory input from the thalamus as well as a feed-forward inhibition from the interneurons.     

Spectrofluorimetric and image recordings of spontaneous and lectin-induced cytosolic calcium oscillations in Jurkat T cells

Intracellular variations in Ca2+ concentrations have been measured in single Jurkat T lymphocyte variants (77 6.8 and E6.1) using Fura-2 as a probe. Under basal conditions, the cytosolic Ca2+ level is stable but some cells show spontaneous Ca2+ oscillations (frequency, 0.30 +/- 0.06 Hz). These oscillations are sensitive to the external concentration of Ca2+ since they can no longer be observed when the bathing solution is replaced (superfusion) with a Ca(2+)-free medium or when a Ca2+ chelator (EGTA) is added. Various changes in the cytosolic concentration of Ca2+ ([Ca2+]i) can be observed when the cells are exposed to the mitogenic lectin phytohemagglutinin (PHA, 80 nM). For instance, in the case of non-oscillating cells, the lectin induces either a rapid increase in [Ca2+]i that is followed by a sustained response (plateau) or it triggers Ca2+ spikes. In the case of experiments done in Ca(2+)-free medium, only the initial spike was observed. In the case of spontaneously oscillating cells, PHA induces a rapid increase in [Ca2+]i that is followed by a plateau where oscillations are absent. In every case, the PHA-dependent Ca2+ response is abrogated in a Ca(2+)-free medium. Computer simulations based on the model of Goldbeter et al. [27] show that the various Ca2+ responses of Jurkat cells are related to the cytosolic level of free Ca2+. Video imaging analyses show that the cellular Ca2+ responses are not homogeneous whether the observations are made in spontaneously oscillating Jurkat cells or when they are exposed to PHA.     

Slow gamma takes the reins in replay

The mechanisms supporting hippocampal memory reactivation are puzzling. Reactivation occurs during ripple oscillations, yet ripples are not coordinated across regions. In this issue of Neuron, Carr et?al. (2012) report that another oscillation, slow gamma, coordinates memory reactivation across the hippocampal network.     

The mechanisms of the formation and the role of the oscillatory activity of the neuronal populations in brain systemic activities

Experimental findings and theoretical concepts that have led to a new insight into the neurophysiological mechanisms underlying information processing and brain state are presented in this review. It is assumed that the brain information processing associated with elementary neuronal assembles is reflected by oscillations in the range of 30-70 Hz and their spatio-temporal organization in millisecond intervals. He functional brain state associated with the non-specific systems is reflected in synchronization or desynchronization of activity of large neuronal populations in the frequency range of 20 Hz.     

Hippocampal ripple oscillations (200 Hz) in mechanisms of memory consolidation

A current status of knowledge about high-frequency (140-200 Hz) ripple oscillations in the CA1 hippocampal subfield is summarized and considered in the context of two-stage model of the hippocampal memory processing. A large body of evidence suggests highly-selective recruitment of pyramidal cells and interneurons in the generation of the oscillatory pattern after co-operative sharp-wave-related discharge of CA3 pyramidal neurons. We also discuss a role of transmission via gap junctions in the mechanisms of ripple oscillations as well as their adaptive aminergic (histaminergic) modulation. Patterns of neuronal firing in the hippocampus observed during ripple oscillations reproduce space-dependant neuronal activity from the previous waking period. Together with a data about efficacy of high-frequency stimulation for induction of synaptic modification it points out a role for ripples in the formation of long-term memory. Focal ultra fast ripples (up to 500 Hz) have been shown to participate in the development of temporal lobe epilepsy.     

Enhanced Stimulus-Induced Gamma Activity in Humans during Propofol-Induced Sedation

Stimulus-induced gamma oscillations in the 30–80 Hz range have been implicated in a wide number of functions including visual processing, memory and attention. While occipital gamma-band oscillations can be pharmacologically modified in animal preparations, pharmacological modulation of stimulus-induced visual gamma oscillations has yet to be demonstrated in non-invasive human recordings. Here, in fifteen healthy humans volunteers, we probed the effects of the GABA_A agonist and sedative propofol on stimulus-related gamma activity recorded with magnetoencephalography, using a simple visual grating stimulus designed to elicit gamma oscillations in the primary visual cortex. During propofol sedation as compared to the normal awake state, a significant 60% increase in stimulus-induced gamma amplitude was seen together with a 94% enhancement of stimulus-induced alpha suppression and a simultaneous reduction in the amplitude of the pattern-onset evoked response. These data demonstrate, that propofol-induced sedation is accompanied by increased stimulus-induced gamma activity providing a potential window into mechanisms of gamma-oscillation generation in humans.