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Distinct firing patterns of neuronal subtypes in cortical synchronized activities.

Cortical neurons, especially GABAergic interneurons, are composed of very diverse subtypes. It remains to be investigated whether each subtype shows a unique firing pattern during the synchronized activities generated by the intracortical circuit. By lowering extracellular Mg(2+) in vitro, we induced NMDA receptor-dependent spontaneous activities in the rat frontal cortex at 30 degrees C. After a series of spontaneous depolarization shifts, the long bursts occurred. The long bursts were composed of initial discharges and fast run-like potentials (FRLP) (4-10 Hz). Large inhibitory currents were induced at the initial discharge. After the strong inhibition decreased, the FRLP started. However, the periodical inhibition survived during the FRLP. At each phase of the synchronized activities, cortical neuron types exhibited distinct firing patterns. Pyramidal cells increased firing frequency periodically up to approximately 25-55 Hz during the FRLP cycles. Fast-spiking (FS) cells fired at the highest frequency in the initial discharge, up to 400 Hz, and could continue firing faster than 200 Hz for several seconds. In the FRLP, the firing frequency of FS cells rhythmically increased up to 150 Hz. In contrast, large cholecystokinin basket cells fired, very similarly to pyramidal cells, at each phase. Somatostatin and vasoactive intestinal polypeptide cells fired faster than pyramidal cells at the initial discharge, but showed the similar firings to pyramidal cells during the FRLP. The firing patterns of cortical neurons are not only determined by the strength and temporal pattern of synchronized inputs but also strongly dependent on the neuronal subtype with specific physiological, chemical, and morphological characteristics.

Action Potentials↗

Structural basis of cortical synchronization. II. Effects of cortical lesions.

1. To understand the structural basis of the different types of interhemispheric synchronizations described in the preceding paper, we made sections of the corpus callosum and lesions of extrastriate cortex. We measured the effects of such operations on the frequency of encounter, width and strength of T, C, and H peaks in cross-correlation histograms computed from single-unit and multiunit recordings from areas 17-18 of opposite cortical hemispheres in the cat. 2. Sectioning of the corpus callosum led to a complete abolition of T and C couplings and a strong reduction of encounter rate and strength of H coupling. A section limited to the posterior half of the corpus callosum abolished T and C couplings completely. This suggests that T and C couplings are mediated by the direct reciprocal connections between visual cortical areas circulating through the posterior part of the corpus callosum. 3. The encounter rate of H peaks depended on the extent of the callosal cut. Larger lesions gave a more pronounced reduction of the number of H peaks. From this observation we conclude that H peaks are at least partially mediated by polysynaptic pathways involving widely distributed cortical regions. 4. Extensive lesions of extrastriate cortex were made by aspiration of the gray matter or injections of ibotenic acid. These lesions removed the direct inputs from cortical areas sending ipsilateral as well as contralateral inputs to the area 17-18 border region. Encounter rate and coupling strength of C and H peaks were decreased, whereas little effect was observed on T peaks. 5. These results demonstrate that all types of interhemispheric synchronization are mediated by corticocortical connections and that T and C peaks are generated by reciprocal connections between areas 17 and 18 of each hemisphere. Feedback connections play a role in mediating or facilitating the C and H types of interhemispheric synchronization.

Animals↗

Cortical synchronization induced by thermal stimulation of the preoptic area in immobilized rats.

Cortical synchronization characterized by frontal spindles and occipital slow wave activity was induced by bilateral thermal stimulation of 2--4 degrees C of the preoptic area in unanaesthetized immobilized rats. The synchronization was demonstrated by ECoG and its power density spectra. The ECoG of the synchronization was similar to that of slow wave sleep. Switching off the thermal stimulation the original activity was recovered in most of the cases. Frontal spindle activity and slow wave activity recorded over the posterior cortex seemed to be dissociated to some degree. Low frequency stimulation at the points of thermal stimulation resulted in frequency following synchronization. In some cases electrical and thermal stimulation induced gradually developing seizure activity.

Animals↗

Proximally targeted GABAergic synapses and gap junctions synchronize cortical interneurons.

Networks of GABAergic interneurons are implicated in synchronizing cortical activity at gamma frequencies (30-70 Hz). Here we demonstrate that the combined electrical and GABAergic synaptic coupling of basket cells instantaneously entrained gamma-frequency postsynaptic firing in layers 2/3 of rat somatosensory cortex. This entrainment was mediated by rapid curtailment of gap junctional coupling potentials by GABAA receptor-mediated IPSPs. Electron microscopy revealed spatial proximity of gap junctions and GABAergic synapses on somata and dendrites. Electrical coupling alone entrained postsynaptic firing with a phase lag, whereas unitary GABAergic connections were ineffective in gamma-frequency phasing. These observations demonstrate precise spatiotemporal mechanisms underlying action potential timing in oscillating interneuronal networks.

Action Potentials↗

Long-range cortical synchronization without concomitant oscillations in the somatosensory system of anesthetized cats.

To determine whether neuronal oscillations are essential for long-range cortical synchronization in the somatosensory system, we characterized the incidence and response properties of gamma range oscillations (20-80 Hz) among pairs of synchronized neurons in primary (SI) and secondary (SII) somatosensory cortex. Synchronized SI and SII discharges, which occurred within a 3 msec period, were detected in 13% (80 of 621) of single-unit pairs and 25% (29 of 118) of multiunit pairs. Power spectra derived from the auto-correlation histograms (ACGs) revealed that approximately 15% of the neurons forming synchronized pairs were characterized by oscillations. Although 24% of the synchronized neuron pairs (19/80) were characterized by oscillations in one or both neurons, only 1% (1/80) of these pairs displayed oscillations at the same frequency in both neurons. Similar results were observed among pairs of multiunit responses. When single-trial responses were analyzed, the vast majority of responses still did not exhibit oscillations in the gamma frequency range. These results suggest that separate populations of cortical neurons can be bound together without being constrained by the phase relationships defined by specific oscillatory frequencies.

Action Potentials↗

Task-related changes in cortical synchronization are spatially coincident with the hemodynamic response.

Using group functional Magnetic Resonance Imaging (fMRI) and group Magnetoencephalography (MEG) we studied two cognitive paradigms: A language task involving covert letter fluency and a visual task involving biological motion direction discrimination. The MEG data were analyzed using an adaptive beam-former technique known as Synthetic Aperture Magnetometry (SAM), which provides continuous 3-D images of cortical power changes. These images were spatially normalized and averaged across subjects to provide a group SAM image in the same template space as the group fMRI data. The results show that frequency-specific, task-related changes in cortical synchronization, detected using MEG, match those areas of the brain showing an evoked cortical hemodynamic response with fMRI. The majority of these changes were event-related desynchronizations (ERDs) in the 5-10 Hz and 15-25 Hz frequency ranges. Our study demonstrates how SAM, spatial normalization, and intersubject averaging enable group MEG studies to be performed. SAM analysis also allows the MEG experiment to have exactly the same task design as the corresponding fMRI experiment. This new analysis framework represents an important advance in the use of MEG as a cognitive neuroimaging technique and also allows mutual cross-validation with fMRI.

Adult↗

Investigating the human mirror neuron system by means of cortical synchronization during the imitation of biological movements.

The human mirror neuron system (MNS) has recently been a major topic of research in cognitive neuroscience. As a very basic reflection of the MNS, human observers are faster at imitating a biological as compared with a non-biological movement. However, it is unclear which cortical areas and their interactions (synchronization) are responsible for this behavioural advantage. We investigated the time course of long-range synchronization within cortical networks during an imitation task in 10 healthy participants by means of whole-head magnetoencephalography (MEG). Extending previous work, we conclude that left ventrolateral premotor, bilateral temporal and parietal areas mediate the observed behavioural advantage of biological movements in close interaction with the basal ganglia and other motor areas (cerebellum, sensorimotor cortex). Besides left ventrolateral premotor cortex, we identified the right temporal pole and the posterior parietal cortex as important junctions for the integration of information from different sources in imitation tasks that are controlled for movement (biological vs. non-biological) and that involve a certain amount of spatial orienting of attention. Finally, we also found the basal ganglia to participate at an early stage in the processing of biological movement, possibly by selecting suitable motor programs that match the stimulus.

Adult↗

Progressive cortical synchronization of ponto-geniculo-occipital potentials during rapid eye movement sleep.

Phasic events, termed ponto-geniculo-occipital potentials, appear in the brainstem, thalamus and cerebral cortex during rapid eye movement sleep. In the cat, the species of choice for ponto-geniculo-occipital studies, these field potentials are usually recorded from the lateral geniculate thalamic nucleus and visual cortex. However, the fact that brainstem cholinergic neurons play a crucial role in the transfer of ponto-geniculo-occipital potentials to the thalamus, coupled with the evidence that mesopontine tegmental neurons project to virtually all thalamic nuclei, together explain why ponto-geniculo-occipital potentials are recorded over widespread territories, beyond the visual thalamocortical system. Here we demonstrate, by means of multi-site unit and field potential recordings from sensory, motor and association cortical areas in behaving cats, that: (i) ponto-geniculo-occipital potentials appear synchronously over the neocortex; and (ii) that their cortical synchronization develops progressively from the period preceding rapid eye movement sleep by 30-90 s (pre-rapid eye movement), to reach the highest degree of intracortical coherence during later epochs of rapid eye movement sleep. We propose that the widespread coherence of cortical ponto-geniculo-occipital potentials underlies the synchronization of fast oscillations (30-40 Hz) during rapid eye movement sleep over many, functionally distinct cortical territories implicated in dreaming, as brainstem-induced ponto-geniculo-occipital-like potentials are consistently followed by such fast oscillations.

Animals↗

Cortical synchronization suggests neural principles of visual feature grouping.

Compositions of visual scenes are related here to neural signals in visual cortex and to cortical circuit models to understand neural mechanisms of perceptual feature grouping. Starting from the hypothesis that synchronization and decoupling of cortical gamma-activities (35-90 Hz) define the relations among visual objects, we concentrate on synchronization related to (1) static retinal stimulation during ocular fixation, and (2) transient stimulation by sudden shifts in object position. The synchronization hypothesis has been tested by analyzing signal correlations in visual cortex of monkeys with the following results: Static retinal stimuli induce loosely phase-coupled gamma-activities among neurons of an object's cortical representation. Patches of gamma-synchronization become decoupled across the representation of an object's contour, and thereby can code figure-ground segregation. Transient stimuli evoke synchronized volleys of stimulus-locked activities that are typically non-rhythmic and include low frequency components in addition to those in the gamma-range. It is argued that stimulus-induced and stimulus-locked synchronizations may play different roles in perceptual feature grouping.

Animals↗

Thiopental uncouples hippocampal and cortical synchronized electroencephalographic activity.

BACKGROUND: Thiopental produces a concentration-dependent continuum of effects on the cortical electroencephalogram (EEG) that has been linked to behavioral measures of anesthetic depth. The complexity of the response, however, limits a clear insight into the neurophysiologic actions of thiopental. The current study investigated thiopental actions on cortical EEG and hippocampal electrical activity, to determine whether similar effects occur on both structures and to compare synchronized activity between these structures. METHODS: Thiopental was administered intravenously via an implanted catheter in freely moving rats. Arterial blood oxygen/carbon dioxide concentration, thiopental concentrations, and temperature were monitored and controlled. Neocortical EEG was recorded from implanted dural surface electrodes and hippocampal neuron electrical activity was recorded from stereotaxically placed microelectrodes. Pharmacokinetic models were used to determine effect site concentrations. RESULTS: Thiopental produced an increase in EEG frequency and amplitude at low concentrations (15-20 micrograms/ml total plasma, approximately 10 microM unbound), which produced a loss of righting reflex. This was followed by a frequency decrease and burst suppression activity at higher concentrations (50-80 micrograms/ml, approximately 60 microM), which produced a loss of tail pinch and corneal reflexes. Higher concentrations of thiopental ( > 60 micrograms/ml) uncoupled synchronized burst discharges recorded in hippocampus and cortex. Isoelectric EEG activity was associated with concentrations of 70-90 micrograms/ml (approximately 80 microM) and a deep level of anesthesia; motor reflexes were abolished, although cardiovascular reflexes remained. In all frequency bands, similar concentration-EEG effect relationships were observed for cortical and hippocampal signals, only differing in the magnitude of response. A reversed progression of effects was observed on recovery. CONCLUSIONS: The results confirm earlier findings in humans and animals and demonstrate that both the hippocampus and neocortex exhibit burst suppression and isoelectric activity during thiopental anesthesia. Thiopental-induced synchronized burst activity was depressed by progressively higher concentrations. The lost synchronization suggests a depression of synaptic coupling between cortical structures contributes to anesthesia.

Anesthetics, Intravenous↗

Synchronous cortical gamma-band activity in task-relevant cognition.

Widespread synchronous oscillatory activity, particularly in the gamma ('40 Hz') band, has been postulated to exist in the brain as a mechanism underlying binding. A new method of examining phase synchronicity across multiple electrode sites in specific EEG frequency bands as a function of time was employed, in a conventional cognitive ERP paradigm in 40 normal subjects. A significant late post-stimulus gamma synchronicity response occurred for task-relevant stimuli, whereas for task-irrelevant stimuli no such response was evident. However, an early response was seen for both task-relevant and irrelevant stimuli. This is the first empirical demonstration that widespread synchronous high frequency oscillations occur in humans in relation to cognition.

Acoustic Stimulation↗

Sleep-wake states and cortical synchronization control by pregnenolone sulfate into the pedunculopontine nucleus.

Cholinergic neurons of the pedunculopontine tegmentum nucleus (PPT) are crucial for initiation and maintenance of electroencephalographic (EEG) desynchronization states like paradoxical sleep and wakefulness. These neurons are regulated by classical neurotransmitter systems from the pontomesencephalic reticular formation and basal ganglia. In addition to this regulation, PPT neuron activity could be modulated by endogenous neurosteroids and particularly by pregnenolone sulfate (PREG-S) because synthesis enzymes of this neurosteroid are present in this area and peripheral administrations of PREG-S affect sleep-wakefulness states. To test this hypothesis, we studied the effects of different doses of PREG-S infusion into the PPT on sleep-wakefulness states in rats. Our results show dose-dependent effects of PREG-S on sleep-wakefulness states. Low concentration of PREG-S (5 ng) increased the amount of paradoxical sleep without any modification of slow wave sleep and wakefulness. High level of PREG-S (10 and 20 ng) increased paradoxical sleep and slow wave sleep together with an increase of delta power and a decrease of theta power during wakefulness. Dependent on the doses used, PREG-S thus can promote paradoxical sleep alone or the global propensity to fall asleep, impairing the quality of wakefulness. These results unveil a new regulation pathway for PPT neurons and strengthen the role of PREG-S in sleep-wakefulness regulation.

Analysis of Variance↗

Dependence of reward contingent positive variation (RCPV) and cortical synchronization on visual input in the cat.

Cats trained to press a lever for milk reward display high amplitude low frequency electrocorticographic post-reinforcement synchronization (PRS) associated with epicortical steady potential shift, termed Reward Contingent Positive Variation (RCPV), over the parieto-occipital cortex. Previously, it was found that the PRS-RCPV phenomenon depends on unpatterned light input devoid of any conceivable information or conditional property. Although training in the dark most likely eliminated the "novelty" factor and the resulting orienting reaction to "light off" as a cause of PRS-RCPV suppression, a possibility could not be excluded that the absence of light had a negatively reinforcing property preventing the emergence of PRS-RCPV. Hence, in the present study an experimental paradigm was used in which "light off" and/or "tone on" cues signalled the availability of reward, the "light off" periods extending through the consummatory response. Seven out of 9 cats, despite 2-4 months of daily training, and 85% correct timing of bar press performance, never showed a PRS-RCPV response (one animal showed only sporadic and poorly developed patterns.) However, when the light was turned on during consumption, in 85% of such tests a fully developed PRS-RCPV emerged in a stimulus-bound manner. One animal was an exception and showed PRS-RCPV both in the absence and presence of light. It was concluded that light input plays a crucial role in the emergence of the PRS-RCPV phenomenon and therefore also participates in the integration of gustatory input.

Animals↗