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Network activity in neurons of the motor and prefrontal areas of the cortex in trained cats in conditions of systemic administration of m-cholinoreceptor blockers.

Experiments on five cats already trained to an operant conditioned food-procuring reflex to light were used to study the network activity of cells in the frontal and motor areas of the cortex accompanying disruption of conditioned reflex behavior in conditions of systemic administration of m-cholinoreceptor blockers. The activity of cortical neurons and their network properties were assessed using auto- and cross-correlation histograms. Doses of central m-cholinoreceptor blockers (the non-selective blocker scopolamine and the relatively selective m1-cholinoreceptor blocker trihexyphenidyl) disrupted performance of the operant motor reflex but had no effect on the appearance of contextual behavior and responses to switching on of the conditioned signal (standing up, elevating the paw). This was accompanied by 1) changes in the patterns of neuron activity in the moor and frontal areas of the cortex, with increases in train, rhythmic, and rhythmic train activity in cortical cells; 2) appearance of synchronicity in the operation of cortical neurons; 3) decreases in the numbers of direct interneuronal connections in the motor and frontal areas of the cortex and in the numbers of connections between these structures.

Animals↗

Scene segmentation by spike synchronization in reciprocally connected visual areas. I. Local effects of cortical feedback.

To investigate scene segmentation in the visual system we present a model of two reciprocally connected visual areas using spiking neurons. Area P corresponds to the orientation-selective subsystem of the primary visual cortex, while the central visual area C is modeled as associative memory representing stimulus objects according to Hebbian learning. Without feedback from area C, a single stimulus results in relatively slow and irregular activity, synchronized only for neighboring patches (slow state), while in the complete model activity is faster with an enlarged synchronization range (fast state). When presenting a superposition of several stimulus objects, scene segmentation happens on a time scale of hundreds of milliseconds by alternating epochs of the slow and fast states, where neurons representing the same object are simultaneously in the fast state. Correlation analysis reveals synchronization on different time scales as found in experiments (designated as tower, castle, and hill peaks). On the fast time scale (tower peaks, gamma frequency range), recordings from two sites coding either different or the same object lead to correlograms that are either flat or exhibit oscillatory modulations with a central peak. This is in agreement with experimental findings, whereas standard phase-coding models would predict shifted peaks in the case of different objects.

Animals↗

Different types of signal coupling in the visual cortex related to neural mechanisms of associative processing and perception.

The hypothesis of object representation by synchronization in the visual cortex has been supported by our recent experiments in monkeys. They demonstrated local synchrony among gamma activities (30-90 Hz) and their perceptual modulation, according to the rules of figure-ground segregation. However, gamma-synchrony in primary visual cortex is restricted to few mm, challenging the synchronization hypothesis for larger cortical object representations. The restriction is due to randomly changing phase relations among locally synchronized patches which, however, form continuous waves of gamma-activity, traveling across object representations. The phase continuity of these waves may support coding of object continuity. Interactions across still larger distances, measured among cortical areas in human data, involve amplitude envelopes of gamma signals. Based on models with spiking neurons we discuss potentially underlying mechanisms. Most important for gamma synchronization are local facilitatory connections with distance-dependent delays. They also explain the occurrence of gamma waves and the restriction of gamma-synchrony. Fast local feedback inhibition generates gamma oscillations and supports local synchrony, while slow shunting inhibitory feedback supports figure-ground segregation. Finally, dispersion in inter-areal far projections destroys coherence of gamma signals, but preserves their amplitude modulations. In conclusion, we propose that the hypothesis of associative processing by gamma synchronization be extended to more general forms of signal coupling.

Action Potentials↗

Increased synchronization of neuromagnetic responses during conscious perception.

In binocular rivalry, the observer views two incongruent images, one through each eye, but is conscious of only one image at a time. The image that is perceptually dominant alternates every few seconds. We used this phenomenon to investigate neural correlates of conscious perception. We presented a red vertical grating to one eye and a blue horizontal grating to the other eye, with each grating continuously flickering at a distinct frequency (the frequency tag for that stimulus). Steady-state magnetic fields were recorded with a 148 sensor whole-head magnetometer while the subjects reported which grating was perceived. The power of the steady-state magnetic field at the frequency associated with a grating typically increased at multiple sensors when the grating was perceived. Changes in power related to perceptual dominance, presumably reflecting local neural synchronization, reached statistical significance at several sensors, including some positioned over occipital, temporal, and frontal cortices. To identify changes in synchronization between distinct brain areas that were related to perceptual dominance, we analyzed coherence between pairs of widely separated sensors. The results showed that when the stimulus was perceived there was a marked increase in both interhemispheric and intrahemispheric coherence at the stimulus frequency. This study demonstrates a direct correlation between the conscious perception of a visual stimulus and the synchronous activity of large populations of neocortical neurons as reflected by stimulus-evoked steady-state neuromagnetic fields.

Adult↗

ERD/ERS patterns reflecting sensorimotor activation and deactivation.

Oscillations in the alpha and beta band (<35 Hz) show characteristic spatiotemporal patterns during sensorimotor processing. Whereas event-related desynchronization (ERD) during motor preparation, execution, and imagery can be seen as a correlate of an activated cortical area, event-related synchronization (ERS) of frequency components between 10 and 13 Hz may represent a deactivated cortical area or inhibited cortical network, at least under certain conditions. Induced beta rhythms (13-35 Hz, beta ERS) can be found in sensorimotor areas following both voluntary movement and somatosensory stimulation. In a recent study we used different tasks involving execution and imagery of movements of the upper and lower limb to produce activation vs. deactivation/inhibition of the sensorimotor hand area. Sensorimotor interference, as a function of the activation level of the motor cortex, was studied by the use of repetitive median nerve stimulation (MNS) (ISI 1.5 s) in 12 healthy volunteers during the following task conditions: (i) cube manipulation between thumb and fingers of one hand, (ii) imagined cube manipulation, (iii) continuous foot rotation movements, and (iv) imagined foot movements. EEG was recorded from hand and foot representation areas and processed time-locked to MNS (ERD/ERS). In addition, task-related band power changes (TRPD/TRPI) were analyzed. We found a clear-cut suppression of the stimulation-induced beta ERS (indicating an enhanced activity state of the sensorimotor areas) during active cube manipulation and a weaker suppression during cube imagery. Mental imagination of foot movement led to an increase of the hand area mu rhythm, but did not interfere with stimulation-related effects on beta ERS. These findings support that interfering sensorimotor activation and deactivation is reflected in graduated changes of induced mu and beta oscillations.

Beta Rhythm↗

Annexins in Paramecium cells. Involvement in site-specific positioning of secretory organelles.

Annexins were isolated from Paramecium cell homogenates by standard ethylene glycol tetraacetic acid (EGTA) extraction and 100 000-g centrifugation. Two different antibodies (Abs) against synthetic peptides were used, Call-15 and B15, which in mammalian cells recognize a sequence of annexin II or a common sequence occurring in several annexins (except for annexin II), respectively. With anti-Call-15 Abs, western blots from EGTA extracts showed strongly reactive bands of 44.5 and 46 kDa and of higher values. Some of these bands bound to the 100 000-g pellet fraction when Ca(2+) was added. Immuno- and affinity labelling revealed selective, Ca(2+)-dependent labelling of the cell cortex, with enrichment around trichocyst docking sites (facing subplasmalemmal Ca(2+) stores). Cortical fluorescence labelling decreased in wild-type (7S) cells when trichocyst ghosts were detached after synchronous exocytosis. Similarly, cortical labelling was reduced when intact trichocysts were detached from the cell surface of non-discharge mutant cells (nd9-28 degrees C, showing identical bands on blots), which then contained numerous heavily labelled phagolysosomes. This strongly suggests annexin downregulation. All together, the dynamic labelling of cortical structures we observed strongly supports involvement of calpactin-like annexins in trichocyst docking. Anti-B15 Abs recognized a band of 51 kDa and some of higher values. These Abs selectively labelled the outlines of the cytoproct, the site of spent phagolysosome exocytosis. In conclusion, our data indicate involvement of specific sets of annexins in site-specific positioning and attachment of widely different secretory organelles at the cell surface in Paramecium cells.

Animals↗

Cyclic assembly-disassembly of cortical microtubules during maturation and early development of starfish oocytes.

An extensive array of cortical microtubules in oocytes of the starfish Pisaster ochraceus undergoes multiple cycles of disappearance and reappearance during maturation and early development. These events were studied in isolated fragments of the oocyte cortex stained with antitubulin antibodies for indirect immunofluorescence. The meshwork of long microtubules is present in the cortex (a) of immature oocytes, i.e., before treatment with the maturation-inducing hormone 1-methyladenine, (b) for 10-20 min after treatment with 1-methyladenine, (c) after formation of the second polar body (in reduced numbers in unfertilized oocytes), and (d) in the intermitotic period between first and second cleavage divisions. The array of cortical microtubules is absent in oocytes (a) undergoing germinal vesicle breakdown, (b) during the two meiotic divisions (polar body divisions), and (c) during mitosis of the first and, perhaps, subsequent cleavage divisions. The cycle of assembly-disassembly of cortical microtubules is synchronized to the cycle of nuclear envelope breakdown and reformation and to the mitotic cycle; specifically, cortical microtubules are present when a nucleus is intact (germinal vesicle, female pronucleus, zygote nucleus, blastomere nucleus) and are absent whenever a meiotic or mitotic spindle is present. These findings are discussed in terms of microtubule organizing centers in eggs, possible triggers for microtubule assembly and disassembly, the eccentric location of the germinal vesicle, and the regulation of oocyte maturation and cell division.

Adenine↗

The epsilon theory: a novel synthesis of the underlying molecular and electrophysiological mechanisms of primary generalized epilepsy and the possible mechanism of action of valproate.

Primary generalized epilepsy may be the result of maldevelopment of central nervous system and each seizure may be the consequence of a neuronal maladaptation to an unknown stimulus using the paleospinothalamical tract due to an overexpression of brain-derived neurotrophic factor and neurotrophin-3. The subsequent protein kinase C epsilon (PKC-epsilon) activation and intracellular Ca(2+) release causes a nociceptive hypersensitization and an increased cortical hyperexcitability because of increased frequency of synchronous Ca(2+) oscillations, cortical maldevelopment at the level of synapses and an attenuation of GABA(A) receptor mediated responses in reticular thalamic nucleus. Valproate may exert its antiepileptic effect as a PKC-epsilon inhibitor, and using with a PKC-epsilon activator that cannot pass blood brain barrier, its side effects may become avoidable.

Calcium↗

Time-dependent cortical asymmetries induced by emotional arousal: EEG analysis of event-related synchronization and desynchronization in individually defined frequency bands.

Event-related desynchronization (ERD) and synchronization (ERS) in the individually defined theta, alpha-1, alpha-2 and alpha-3 frequency bands were measured in 20 healthy subjects in response to International Affective Picture System (IAPS) stimuli with low, moderate and high arousal (LA, MA and HA) content. The 62-channel EEG, skin conductance response (SCR) and heart rate (HR) were simultaneously recorded while subjects viewed sequentially presented pictures and subjectively rated them after each presentation. In the theta band, both MA and HA vs. LA stimuli induced larger synchronization over the left anterior and bilaterally over posterior cortical leads. However, rather unexpectedly, both MA and HA vs. LA stimuli yielded larger alpha-1 synchronization, predominantly over occipital leads. In both theta and alpha-1 bands, affectively salient stimuli prompted larger ERS against the background of the overall dominance in power synchronization of posterior regions of the right hemisphere, irrespective of stimulus category. Finally, in the alpha-3 band, HA stimuli induce a lateralized time-dependent power increase over anterior leads of the left hemisphere. The hemispheric asymmetries revealed point to recruitment of not only posterior regions of the right hemisphere (theta and alpha-1 bands), but also of anterior regions of the left hemisphere (theta and alpha-3 bands) in affect analysis beyond valence dimension. In terms of affective chronometry, the significant arousalxtime interactions clearly indicate that in the theta frequency band discrimination of affective stimuli has already started at 200 ms post-stimulus, whereas in the alpha-1 and alpha-3 bands this process is delayed by up to 800-1200 ms.

Adolescent↗

CO2-stimulated NaCl absorption in the mouse renal cortical thick ascending limb of Henle. Evidence for synchronous Na +/H+ and Cl-/HCO3- exchange in apical plasma membranes.

These experiments evaluated salt transport processes in isolated cortical thick limbs of Henle (cTALH) obtained from mouse kidney. When the external solutions consisted of Krebs-Ringer bicarbonate (KRB), pH 7.4, and a 95% O2-5% CO2 gas phase, the spontaneous transepithelial voltage (Ve, mV, lumen-to-bath) was approximately mV; the net rate of Cl- absorption (JnetCl) was approximately 3,600 pmols s-1 cm-2; the net rate of osmotic solute absorption Jnetosm was twice JnetCl; and the net rate of total CO2 transport (JnetCO2) was indistinguishable from zero. Thus, net Cl- absorption was accompanied by the net absorption of a monovalent cation, presumably Na+, and net HCO3- absorption was negligible. This salt transport process was stimulated by (CO2 + HCO3-): omission of CO2 from the gas phase and HCO3- from external solutions reduced JnetCl, Jnetosm, and Ve by 50%. Furthermore, 10(-4) M luminal furosemide abolished JnetCl and Ve entirely. The lipophilic carbonic anhydrase inhibitor ethoxzolamide (10(-4) M, either luminal or peritubular) inhibited (CO2 + HCO3-)-stimulated JnetCl, Jnetosm, and Ve by approximately 50%; however, when the combination (CO2 + HCO3-) was absent, ethoxzolamide had no detectable effect on salt transport. Ve was reduced or abolished entirely by omission of either Na+ or Cl- from external solutions, by peritubular K+ removal, by 10(-3) M peritubular ouabain, and by 10(-4) M luminal SITS. However, Ve was unaffected by 10(-3) M peritubular SITS, or by the hydrophilic carbonic anhydrase inhibitor acetazolamide (2.2 x 10(-4) M, lumen plus bath). We interpret these data to indicate that (CO2 + HCO3-)-stimulated NaCl absorption in the cTALH involved two synchronous apical membrane antiport processes: one exchanging luminal Na+ for cellular H+; and the other exchanging luminal Cl- for cellular HCO3- or OH-, operating in parallel with a (CO2+ HCO3-)-independent apical membrane NaCl cotransport mechanism.

Absorption↗

Influence of low and high frequency inputs on spike timing in visual cortical neurons.

Cortical neurons in vivo respond to sensory stimuli with the generation of action potentials that can show a high degree of variability in both their number and timing with repeated presentations as wells as, on occasion, a high degree of synchronization with other cortical neurons, including in the gamma frequency range of 30-70 Hz. Here we examined whether or not this variability may arise from the intrinsic mechanisms of action potential generation in cortical regular spiking, fast spiking and intrinsic burst-generating neurons maintained in vitro. For this purpose, we performed intracellular recordings in slices of ferret visual cortex and activated these cells with the intracellular injection of various current waveforms. Some of these waveforms were derived from barrages of postsynaptic potentials evoked by visual stimulation recorded in vivo; others were artificially created and contained various amounts of gamma range fluctuations; finally, others consisted of swept-sinewave current (ZAP current) functions. Using such stimuli, we found that, as expected given the resistive and capacitive properties of cortical neurons, low frequencies have a larger effect on the membrane potential of cortical neurons than do higher frequencies. However, increasing the amount of gamma range fluctuations in a stimulus leads to more precise timing of action potentials. This suggests that different frequencies play different roles, low frequencies being efficient for depolarizing cells with high frequencies increasing the precision of action potential timing. In parallel to increases in temporal precision, the addition of higher frequency components increases the range of interspike intervals present in the action potential discharge. These results suggest that higher frequency components such as gamma range fluctuations may facilitate the generation of action potentials with a high temporal precision while at the same time exhibiting a high degree of variability in interspike intervals on single trials. This temporal precision may facilitate the use of temporal codes or the generation of precise synchronization for the transmission and analysis of information within cortical networks.

Action Potentials↗

Cortical network resonance and motor activity in humans.

Large areas of the human motor cortex are devoted to the control of the contralateral hand and forearm. Just how activities scattered across these motor areas may be brought together in the execution of a given movement remains unclear. There is increasing evidence, largely from animal studies, suggesting that sensory integration involves the synchronization of activity between spatially distributed cortical sites. Here we review recent evidence that cortical activity becomes oscillatory and synchronized between spatially distributed sites during performance of a movement in humans. Cortico-cortical synchronization may occur with a precision in the millisecond range, is essentially limited to those cortical elements active in a given task, and changes in both its distribution and frequency in a task-related manner. Synchronization at specific frequencies may therefore link disparate cortical activities into the functional ensembles underlying voluntary movement in humans.

Animals↗

Timing of major ontogenetic events in the visual cortex of the rhesus monkey.

The place and time of origin, the migration and eventual disposition of neurons of the monkey visual cortex were studied by autoradiography in animals killed at various intervals after 3H-thymidine pulse labeling at embryonic (E) and early postnatal (P) stages. All neurons destined for the visual cortex are generated during about a 2-month period between E45 and E102. Neuron position in the cortical laminae correlates systematically with time of cell origin; neurons destined for deeper cortical positions are generated earlier, and more superficial ones progressively later. Thus, most neurons in layer VI are born between E45 and E60, in layer V between E60 and E70, in layer IV between E70 and E80, and in layers III and II between E80 and E102. No neurons, but numerous glia, are generated within the cortical plate itself. Initially young neurons are produced almost exclusively in the ventricular zone. Later they are probably generated in both ventricular and subventricular zones, and by the end of the proliferative period the subventricular zone becomes the predominant source of new cells. At the time when all neurons destined for the monkey visual cortex have already been produced, primary fissures are barely indicated on the cerebral surface and no secondary fissure appears as yet. Autoradiographic analyses indicate that at early stages young neurons move to the cortical plate relatively synchronously and at a fast rate, whereas at later stages there are considerable differences in the rates of cell migration. At early stages when the migration pathway is relatively short, the external process of the ventricular cell may stretch across almost the entire migratory distance. It is possible that nuclei move without interruption within their own cylinders of cytoplasm, a mechanism which might account for the rapid, synchronous movement of cell bodies as seen in the autoradiographic material. During later stages when young neurons, mostly of subventricular origin, move across a distance which is more than 10 times the length of their leading process, migrating cells follow radial glial guides across the widened intermediate zone and through densely packed cortical plate. This type of cell displacement seems to proceed less synchronously and require more time. It is proposed that two different mechanisms of cell displacement might exist: one in operation at early stages of cortical formation when mostly ventricular cells migrate, and another utilized by subventricular cells at later stages.

Animals↗

Neuronal assembly dynamics in the rat auditory cortex during reorganization induced by intracortical microstimulation.

Single neurons, acting alone, cannot account for the complex and rapid computations that are routinely accomplished by the behaving nervous system. Recent studies with separable multineuron recordings are showing that neuronal assemblies can indeed be detected and that their organization is very dynamic, depending on variables such as time, physical stimulus, and context. Here we explore both single-neuron and assembly properties in the rat's auditory cortex. Acoustic stimuli are used as a normal, physiological input, and weak electrical intracortical microstimulation (ICMS) as a perturbation that forces a rapid cortical reorganization. In this setting, various aspects of neuronal interactions are changed by the ICMS. We found that cortical neurons exhibited highly synchronous oscillatory firing patterns that were enhanced by ICMS. Cross-correlation studies between two spike trains showed that statistically significant correlations depended on the anatomical distance between the two neurons. ICMS changed the strength and the local number of such correlations. Joint petristimulus analysis and gravity analysis showed that the correlation between neuronal activities varied dynamically at several time scales. We have identified neuronal assemblies in two ways, defined through similarity of receptive field properties and defined through correlated firing. Close anatomical spacing between neurons was conducive to, but not sufficient for membership in, the same assembly with either definition. ICMS changed cortical organization by altering assembly membership. Our data show that neuronal assemblies in the rat auditory cortex can be established transiently in time and that their membership is dynamic.

Acoustic Stimulation↗

Changes in cortical and hippocampal EEG activity accompanying spontaneous electrocortical seizures in rats.

The purpose of the present study was to find out whether the occurrence of bursts of spontaneous spike-wave discharges (SWD) in rat neocortex is related to a particular state of vigilance (level of arousal), as some authors suggested, or rather to transitions from one state to another as postulated by others. Patterns of cortical and hippocampal EEG preceding and following the SWD bursts were studied in rats. It has been found that the beginning of an SWD episode is usually preceded by a shift of cortical activity toward synchronization and replacement of the rhythmic slow activity (RSA) in the hippocampus by large irregular activity (LIA). After SWD, the cortical activity is usually more desynchronized and RSA is present more frequently than just before its onset. An analysis of selected episode-free and episode-rich EEG segments revealed that SWD's occur in abundance at the periods characterized by frequent changes of the hippocampal EEG pattern but are absent during the periods in which long-lasting RSA trains dominate in the record. Thus, the data confirm that SWD occurrence is related more to transitions from one state to another than to a particular state as such. They also indicate that the preferable conditions for SWD's appear when arousal is decreasing from a moderate to a lower level.

Animals↗

Synchronization of fast (30-40 Hz) spontaneous oscillations in intrathalamic and thalamocortical networks.

The synchronization of fast (mainly 30 to 40 Hz) oscillations in intrathalamic and thalamocortical (TC) networks of cat was studied under ketamine-xylazine anesthesia and in behaving animals by means of field potential, extra- and intracellular recordings from multiple sites in the thalamic reticular (RE) nucleus, dorsal (sensory, motor, and intralaminar) thalamic nuclei, and related neocortical areas. Far from being restricted to tonically activated behavioral states, the fast oscillations also appeared during resting sleep and deep anesthesia, when they occurred over the depolarizing component of the slow (<1 Hz) oscillation and were suppressed during the prolonged hyper-polarizations of RE, TC, and cortical neurons. The synchronization of fast rhythms among different thalamic foci was robust. Fast rhythmic cortical waves and subthreshold depolarizing potentials in TC neurons were highly coherent; however, the synchronization of the fast oscillation required recordings from reciprocally related neocortical and thalamic foci, as identified by monosynaptic responses in both directions. The short-range spatial confinement of coherent fast rhythms contrasted with the large-scale synchronization of low-frequency sleep rhythms. Transient fast rhythms, appearing over the depolarizing envelope of the slow sleep oscillation, became sustained when brain activation was elicited by stimulation of mesopontine cholinergic nuclei or during brain-active behavioral states in chronic experiments. These data demonstrate that fast rhythms are part of the background electrical activity of the brain and that desynchronization, used to designate brain-active states, is an erroneous term inasmuch as the fast oscillations are synchronized not only in intracortical but also in intrathalamic and TC networks.

Action Potentials↗

Frequency of synchronous oscillations of neuronal activity increases during development and is correlated to the number of synapses in cultured cortical neuron networks.

It has been proposed that synchronous oscillations of groups of neurons corresponding to sensory information and changes in temporal pattern of oscillations are important for processing of the information in the cortex. However, it has not been determined yet how the temporal or spatial pattern of such oscillations are regulated. We observed spontaneous synchronous oscillations of Ca2+ transients, which were caused by bursts of action potentials of neurons, even in cultured cortical neurons. The frequency of synchronous Ca2+ oscillations increased with development of synapses in cultured neurons and was highly correlated to the number of synapses formed in the same culture.

Animals↗

[Electrocortico- and electrosubcorticographic correlates of temporal epilepsy seizures].

Results of studying the electrographic cortical and subcortical correlates of temporal epilepsy seizures in 23 patients with complicated forms of the disease are presented. To these patients permanent intracerebral electrodes were implanted stereotaxically into the cortical, limbic and thalamic structures of both hemispheres: this was done for both diagnostic and therapeutic purposes. A comparison of the clinical and electrographic manifestations of the seizures showed that the aura correlated with the desynchronization reaction in the deep and cortical structures; seizures of automatism, temporal pseudo-absences, vegetovisceral and polymorphic focal attacks took their course with synchronized epileptic activity in the cortical and limbic structures. Tonico-clonic convulsive seizures may take place with epileptic activity registered in individual structures. A systematized cerebral organization of the temporal epilepsy seizures which are realized by a complex of cortical, limbic and truncal structures is suggested.

Amygdala↗