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Recurrent excitatory postsynaptic potentials induced by synchronized fast cortical oscillations.

Gamma frequency (about 20-70 Hz) oscillations occur during novel sensory stimulation, with tight synchrony over distances of at least 7 mm. Synchronization in the visual system has been proposed to reflect coactivation of different parts of the visual field by a single spatially extended object. We have shown that intracortical mechanisms, including spike doublet firing by interneurons, can account for tight long-range synchrony. Here we show that synchronous gamma oscillations in two sites also can cause long-lasting (>1 hr) potentiation of recurrent excitatory synapses. Synchronous oscillations lasting >400 ms in hippocampal area CA1 are associated with an increase in both excitatory postsynaptic potential (EPSP) amplitude and action potential afterhyperpolarization size. The resulting EPSPs stabilize and synchronize a prolonged beta frequency (about 10-25 Hz) oscillation. The changes in EPSP size are not expressed during non-oscillatory behavior but reappear during subsequent gamma-oscillatory events. We propose that oscillation-induced EPSPs serve as a substrate for memory, whose expression either enhances or blocks synchronization of spatially separated sites. This phenomenon thus provides a dynamical mechanism for storage and retrieval of stimulus-specific neuronal assemblies.

Animals↗

Network modulation of a slow intrinsic oscillation of cat thalamocortical neurons implicated in sleep delta waves: cortically induced synchronization and brainstem cholinergic suppression.

A slow (0.5-4 Hz) oscillation of thalamic neurons was recently described and attributed to the interplay of two intrinsic currents. In this study, we investigated the network modulation of this intrinsic thalamic oscillation within the frequency range of EEG sleep delta-waves. We performed intracellular and extracellular recordings of antidromically identified thalamocortical cells (n = 305) in sensory, motor, associational, and intralaminar nuclei of anesthetized cats. At the resting membrane potential, Vm (-60.3 +/- 0.4 mV, mean +/- SE), cortical stimulation induced spindle-like oscillations (7-14 Hz), whereas at Vm more negative than -65 mV the same stimuli triggered an oscillation within the EEG delta-frequency (0.5-4 Hz), consisting of low-threshold spikes (LTSs) followed by after hyperpolarizing potentials (AHPs). The LTS-AHP sequences outlasted cortical stimuli as a self-sustained rhythmicity at 1-2 Hz. Corticothalamic stimuli were able to transform subthreshold slow (0.5-4 Hz) oscillations, occurring spontaneously at Vm more negative than -65 mV, into rhythmic LTSs crowned by bursts of Na+ spikes that persisted for 10-20 sec after cessation of cortical volleys. Cortical volleys also revived a hyperpolarization-activated slow oscillation when it dampened after a few cycles. Auto- and crosscorrelograms of neuronal pairs revealed that unrelated cells became synchronized after a series of corticothalamic stimuli, with both neurons displaying rhythmic (1-2 Hz) bursts or spike trains. Since delta-thalamic oscillations, prevailing during late sleep stages, are triggered at more negative Vm than spindles characterizing the early sleep stage, we postulate a progressive hyperpolarization of thalamocortical neurons with the deepening of the behavioral state of EEG-synchronized sleep. In view of the evidence that cortical-elicited slow oscillations depend on synaptically induced hyperpolarization of thalamocortical cells, we propose that the potentiating influence of the corticothalamic input results from the engagement of two GABAergic thalamic cell classes, reticular and local-circuit neurons. The thalamocorticothalamic loop would transfer the spike bursts of thalamic oscillating cells to cortical targets, which in turn would reinforce the oscillation by direct pathways and/or indirect projections relayed by reticular and local-circuit thalamic cells. Stimulation of mesopontine cholinergic [peribrachial (PB) and laterodorsal tegmental (LDT)] nuclei in monoamine-depleted animals had an effect that was opposite to that exerted by corticothalamic volleys. PB/LDT stimulation reduced or suppressed the slow (1-4 Hz) oscillatory bursts of high-frequency spikes in thalamic cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Local circuit interactions in synchronization of cortical neurones.

Under certain circumstances large numbers of neurones in the mammalian central nervous system (CNS) can discharge simultaneously. An example of such activity is recorded from a hippocampal slice in the presence of agents which block synaptic inhibition. This synchronized discharge occurs spontaneously in a rhythmic fashion or may be triggered by stimulation of any afferent pathway. Its generation appears to involve local circuit interactions. The favourable conditions offered by an in vitro preparation have allowed the cellular events during this activity to be examined in some detail. Three factors appear to be critically involved in the synchronization process. Firstly, the intrinsic ability of neurones to generate bursts, secondly, the existence of powerful recurrent excitatory connections, and thirdly the absence of inhibition which normally prevents the spread of bursting activity through the recurrent connections. Computer simulations show that in a sparsely connected network of bursting neurones activity initiated in a few cells may spread through recurrent connections until eventually the whole population discharges simultaneously. Rhythmic discharges similar to those described here also underly various CNS functions including centrally-originating motor patterns. It remains to be determined whether neuronal properties and connectivity found to be important in this hippocampal rhythm may also play a role in the generation of other rhythmic activities in the mammalian CNS.

Animals↗

Transmission through the dorsal spinocerebellar and spinoreticular tracts: wakefulness versus thiopental anesthesia.

BACKGROUND: Most of what is known regarding the actions of injectable barbiturate anesthetics on the activity of lumbar sensory neurons arises from experiments performed in acute animal preparations that are exposed to invasive surgery and neural depression caused by coadministered inhalational anesthetics. Other parameters such as cortical synchronization and motor ouflow are typically not monitored, and, therefore, anesthetic actions on multiple cellular systems have not been quantitatively compared. METHODS: The activities of antidromically identified dorsal spinocerebellar and spinoreticular tract neurons, neck motoneurons, and cortical neurons were monitored extracellularly before, during, and following recovery from the anesthetic state induced by thiopental in intact, chronically instrumented animal preparations. RESULTS: Intravenous administration of 15 mg/kg, but not 5 mg/kg, of thiopental to awake cats induced general anesthesia that was characterized by 5-10 min of cortical synchronization, reflected as large-amplitude slow-wave events and neck muscle atonia. However, even though the animal behaviorally began to reemerge from the anesthetic state after this 5-10-min period, neck muscle (neck motoneuron) activity recovered more slowly and remained significantly suppressed for up to 23 min after thiopental administration. The spontaneous activity of both dorsal spinocerebellar and spinoreticular tract neurons was maximally suppressed 5 min after administration but remained significantly attenuated for up to 17 min after injection. Peripheral nerve and glutamate-evoked responses of dorsal spinocerebellar and spinoreticular tract neurons were particularly sensitive to thiopental administration and remained suppressed for up to 20 min after injection. CONCLUSIONS: These results demonstrate that thiopental administration is associated with a prolonged blockade of motoneuron output and sensory transmission through the dorsal spinocerebellar and spinoreticular tracts that exceeds the duration of general anesthesia. Further, the blockade of glutamate-evoked neuronal responses indicates that these effects are due, in part, to a local action of the drug in the spinal cord. The authors suggest that this combination of lumbar sensory and motoneuron inhibition underlies the prolonged impairment of reflex coordination observed when thiopental is used clinically.

Afferent Pathways↗

Plasticity of orientation preference maps in the visual cortex of adult cats.

In contrast to the high degree of experience-dependent plasticity usually exhibited by cortical representational maps, a number of experiments performed in visual cortex suggest that the basic layout of orientation preference maps is only barely susceptible to activity-dependent modifications. In fact, most of what we know about activity-dependent plasticity in adults comes from experiments in somatosensory, auditory, or motor cortex. Applying a stimulation protocol that has been proven highly effective in other cortical areas, we demonstrate here that enforced synchronous cortical activity induces major changes of orientation preference maps (OPMs) in adult cats. Combining optical imaging of intrinsic signals and electrophysiological single-cell recordings, we show that a few hours of intracortical microstimulation (ICMS) lead to an enlargement of the cortical representational zone at the ICMS site and an extensive restructuring of the entire OPM layout up to several millimeters away, paralleled by dramatic changes of pinwheel numbers and locations. At the single-cell level, we found that the preferred orientation was shifted toward the orientation of the ICMS site over a region of up to 4 mm. Our results show that manipulating the synchronicity of cortical activity locally without invoking training, attention, or reinforcement, OPMs undergo large-scale reorganization reminiscent of plastic changes observed for nonvisual cortical maps. However, changes were much more widespread and enduring. Such large-scale restructuring of the visual cortical networks indicates a substantial capability for activity-dependent plasticity of adult visual cortex and may provide the basis for cognitive learning processes.

Age Factors↗

Feed-forward synchronization: propagation of temporal patterns along the retinothalamocortical pathway.

Visual responses in the cortex and lateral geniculate nucleus (LGN) are often associated with synchronous oscillatory patterning. In this short review, we examine the possible relationships between subcortical and cortical synchronization mechanisms. Our results obtained from simultaneous multi-unit recordings show strong synchronization of oscillatory responses between retina, LGN and cortex, indicating that cortical neurons can be synchronized by oscillatory activity relayed through the LGN. This feed-forward synchronization mechanism operating in the 60 to 120 Hz frequency range was observed mostly for static stimuli. In response to moving stimuli, by contrast, cortical synchronization was independent of oscillatory inputs from the LGN, with oscillation frequency in the range of 30 to 60 Hz. The functional implications of synchronization of activity from parallel channels are discussed, in particular its significance for signal transmission and cortical integration processes.

Animals↗

The functional significance of gap junction channels in the epileptogenicity and seizure susceptibility of juvenile rats.

PURPOSE: The functional significance of gap-junction (GJ) channels in seizure susceptibility and induction and maintenance of seizures in the developing rat brain was investigated on the 4-aminopyridine (4-AP) in vivo epilepsy model. METHODS: In electrophysiological experiments, GJs were manipulated with a blocker or opener before induction or at the active epileptic foci between postnatal days 9 and 28 (P9-28). Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) amplification was used to measure the levels of connexin (Cx) 26, 32, 36, and 43 mRNAs at the untreated cortex or epileptic foci. RESULTS: The basic electrocorticogram (ECoG) and Cx messenger RNA (mRNA) expression patterns exhibited characteristic maturation; the 4-AP-induced epileptiform activity correlated well with these changes. Cx mRNA expressions were significantly upregulated around P16 (except for Cx26). The Cx26, 36, and 43 gene inducibility was highest around P16 and then declined significantly. In the youngest animals, the GJ opener induced rhythmic synchronous cortical activity. On maturation, the seizures became focalized and periodic; the discharges accelerated their amplitude and frequency increase. A transient decrease (P13-14) and then increase (P15-16) in seizure susceptibility were followed by a tendency to periodicity and focalization. CONCLUSIONS: The study suggests that GJ communication is involved in rhythm genesis and synchronization of cortical activity and may enhance the epileptogenicity of the developing brain.

4-Aminopyridine↗

Distraction affects frontal alpha rhythms related to expectancy of pain: an EEG study.

Previous electroencephalographic (EEG) evidence has shown event-related desynchronization (ERD) of alpha rhythms before predictable painful stimuli, as a possible neural concomitant of attentional preparatory processes (Babiloni, C., Brancucci, A., Babiloni, F., Capotosto, P., Carducci, F., Cincotti, F., Arendt-Nielsen, L., Chen, A.C., Rossini, P.M., 2003. Anticipatory cortical responses during the expectancy of a predictable painful stimulation. A high-resolution electroencephalography study. Eur. J. Neurosci. 18 (6) 1692-700). This study tested the hypothesis that alpha ERD before predictable painful stimuli is reduced as an effect of distraction. A visual warning stimulus preceded a laser painful stimulation, which was strictly followed by visual imperative stimuli. In the Pain (control) condition, no task was required after the imperative stimuli. In the Pain + Movement condition, subjects had to perform a movement of the right index finger. In the Pain + Cognition condition, they had to mentally perform an arithmetical task. EEG data were recorded in 10 subjects from 30 electrodes. Artifact-free recordings were spatially enhanced by surface Laplacian transformation. Alpha ERD was computed at three alpha sub-bands according to subjects' individual alpha frequency peak (i.e., about 6-8 Hz, 8-10 Hz, 10-12 Hz). Compared to the control condition, the subjects reported a significantly lower stimulus intensity perception and unpleasantness in the Pain + Movement and Pain + Cognition conditions. In addition, there was a cancellation of the alpha 3 ERD (i.e., about 10-12 Hz) in Pain + Cognition condition and even a generation of a statistically significant alpha 3 ERS in Pain + Movement condition. These effects were maximum over fronto-central midline. These results suggest that distraction during the expectancy of pain is related to a reduced neural desynchronization of fronto-central midline alpha rhythms (i.e., reduced cortical activation) towards an overt hyper-synchronization (cortical idling).

Adult↗

Hipnic modulation of cerebellar information processing: implications for the cerebro-cerebellar dialogue.

Recent evidence indicates that during the sleep-waking cycle the forebrain and the cerebellum show parallel changes of their operating capabilities and suggest that cooperation between these two structures plays a different role in the different behavioral states. In particular, a high degree of cerebro-cerebellar cooperation is expected in waking and in paradoxical sleep when enhanced information processing within the cerebellum and the cortex is associated with effective reciprocal cerebro-cerebellar signal transmission. We first speculate that during waking, a state in which a wide range of behaviors is produced by the interaction with the external world, the cerebellum might assist the cortex to develop the neural dynamic patterns which underlie behaviors and that this could be accomplished via cerebellar modulation of both short- and long-range cortical synchronization. In particular, we propose that the cerebellum might favour the automatic triggering of the patterns already acquired, when requested by the context, as well as the acquisition of novel patterns, when found to be of adaptive value, and might even modulate the access to consciousness of brain operations, if producing unpredicted results, by regulating pattern complexity. This proposal is based on the experimental evidence that oscillatory activity may flow within the cerebro-cerebellar loops and that stimulation or lesion of the cerebellar structures affects cortical synchronization. Then we report evidence indicating that during paradoxical sleep, when brain activation occurs in the absence of sensory inflow and motor output, cerebro-cerebellar cooperation mainly favours consolidation of newly acquired waking patterns and/or savings of old patterns from disruption possibly through a non-utilitarian replay process. Finally, we propose that cerebro-cerebellar cooperation weakens during slow wave sleep, given that in this sleep state neuronal activity and excitability decrease both in the cerebellum and in the forebrain and cerebello-cortical signal transmission is at least partially gated at the thalamic level.

Animals↗

Synchronization of visual responses between the cortex, lateral geniculate nucleus, and retina in the anesthetized cat.

Synchronization of spatially distributed responses in the cortex is often associated with periodic activity. Recently, synchronous oscillatory patterning was described for visual responses in retinal ganglion cells that is reliably transmitted by the lateral geniculate nucleus (LGN), raising the question of whether oscillatory inputs contribute to synchronous oscillatory responses in the cortex. We have made simultaneous multi-unit recordings from visual areas 17 and 18 as well as the LGN and the retina to examine the interactions between subcortical and cortical synchronization mechanisms. Strong correlations of oscillatory responses were observed between retina, LGN, and cortex, indicating that cortical neurons can become synchronized by oscillatory activity relayed through the LGN. This feedforward synchronization occurred with oscillation frequencies in the range of 60-120 Hz and was most pronounced for responses to stationary flashed stimuli and more frequent for cells in area 18 than in area 17. In response to moving stimuli, by contrast, subcortical and cortical oscillations dissociated, proving the existence of independent subcortical and cortical mechanisms. Subcortical oscillations maintained their high frequencies but became transient. Cortical oscillations were now dominated by a cortical synchronizing mechanism operating in the 30-60 Hz frequency range. When the cortical mechanism dominated, LGN responses could become phase-locked to the cortical oscillations via corticothalamic feedback. In summary, synchronization of cortical responses can result from two independent but interacting mechanisms. First, a transient feedforward synchronization to high-frequency retinal oscillations, and second, an intracortical mechanism, which operates in a lower frequency range and induces more sustained synchronization.

Animals↗

The synchronization of the human cortical working memory network.

A verbal reasoning problem at the intersection of verbal working memory, problem-solving, and language comprehension was examined using event-related fMRI to distinguish differences in the differential timing of the response of the various cortical regions that compose the working memory network. Problems were developed such that the process demand as well as the timing of the manipulation of the contents of working memory (i.e., a demanding computation) was varied. Activation was observed in several regions including the dorsolateral prefrontal cortex, the inferior frontal gyrus, and the parietal lobe. Examination of the MR amplitude response revealed that the regions do not all activate simultaneously; instead, their activation time courses reveal differential responses that correspond to their theoretical processing role in the problem-solving task. The coordination of cortical area responses reveals how the various cortical regions synchronize and collaborate in order to accomplish a given cognitive function.

Adult↗

Fast (mainly 30-100 Hz) oscillations in the cat cerebellothalamic pathway and their synchronization with cortical potentials.

1. Intracellular recordings from 216 thalamocortical (TC) neurones in the ventrolateral (VL) nucleus of intact-cortex and decorticated cats under ketamine-xylazine anaesthesia revealed spontaneously occurring fast oscillations (mainly 30-100 Hz) in 86% of investigated cells. The fast depolarizing events consisted of excitatory postsynaptic potentials (EPSPs), giving rise to fast prepotentials (FPPs) in 22% of neurones, which eventually lead to full-blown action potentials. The frequency of fast events changed by factors of 2-5 in periods as short as 0.3-1.0 s. 2. The spontaneous oscillations were similar to responses evoked in VL relay neurones by stimuli to the afferent cerebellofugal axons in brachium conjunctivum (BC) and were strikingly reduced or abolished after electrolytic lesion of BC axons. 3. The amplitude and duration of fast depolarizing events were significantly reduced during the descending phase of the inhibitory postsynaptic potentials (IPSPs) in TC cells, related to spontaneous spindles or evoked by local thalamic stimulation. 4. Averaged field potentials recorded from motor cortex and triggered by EPSPs and/or action potentials of intracellularly recorded VL cells demonstrated that both spontaneous and BC-evoked fast depolarizations in VL relay neurones were coherent with fast rhythms in cortical area 4. 5. These results show that, in addition to the thalamic and cortical generation sites of the fast (so-called gamma) oscillations, prethalamic relay stations, such as deep cerebellar nuclei, are major contributors to the induction of fast rhythms which depend on the depolarization of thalamic and cortical neurones and which represent a hallmark of brain activation patterns.

Action Potentials↗

Effects of prolonged waking-auditory stimulation on electroencephalogram synchronization and cortical coherence during subsequent slow-wave sleep.

Evidence suggests that sleep homeostasis is not only dependent on duration of previous wakefulness but also on experience- and/or use-dependent processes. Such homeostatic mechanisms are reflected by selective increases in the duration of a sleep stage, modifications to electrophysiological-metabolic brain patterns in specific sleep states, and/or reactivation to neuronal ensembles in subsequent sleep periods. Use-dependent sleep changes, apparently different from those changes caused by memory consolidation processes, are thought to reflect neuronal restoration processes after the sustained exposure to stimulation during the preceding wakefulness. In the present study, we investigated changes in the brain electrical activity pattern during human sleep after 6 hr of continuous auditory stimulation during previous wakefulness. Poststimulation nights showed a widespread increase of spectral power within the alpha (8-12 Hz) and sleep spindle (12-15 Hz) frequency range during slow-wave sleep (SWS) compared with the baseline night. This effect was mainly attributable to an enhanced EEG amplitude rather than an increase of oscillations, except for temporal (within alpha and sleep spindles) and parietal regions (within sleep spindles) in which both parameters contributed equally to the increase of spectral energy. Power increments were accompanied by a strengthening of the coherence between fronto-temporal cortical regions within a broad frequency range during SWS but to the detriment of the coherence between temporal and parieto-occipital areas, suggesting underlying compensatory mechanisms between temporal and other cortical regions. In both cases, coherence was built up progressively across the night, although no changes were observed within each SWS period. No electrophysiological changes were found in rapid eye movement sleep. These results point to SWS as a critical brain period for correcting the cortical synaptic imbalance produced by the predominant use of specific neuronal populations during the preceding wakefulness, as well as for synaptic reorganization after prolonged exposure to a novel sensory experience.

Acoustic Stimulation↗