Oscillatory Network Activity Research Articles

Oscillatory activity in the neural networks of spiking elements

We study the dynamics of activity in the neural networks of enhanced integrate-and-fire elements (with random noise, refractory periods, signal propagation delay, decay of postsynaptic potential, etc.). We consider the networks composed of two interactive populations of excitatory and inhibitory neurons with all-to-all or random sparse connections. It is shown by computer simulations that the regime of regular oscillations is very stable in a broad range of parameter values. In particular, oscillations are possible even in the case of very sparse and randomly distributed inhibitory connections and high background activity. We describe two scenarios of how oscillations may appear which are similar to Andronov–Hopf and saddle-node-on-limit-cycle bifurcations in dynamical systems. The role of oscillatory dynamics for information encoding and processing is discussed.

In VivoLabeling of Parvalbumin-Positive Interneurons and Analysis of Electrical Coupling in Identified Neurons

GABAergic interneurons can pace the activity of principal cells and are thus critically involved in the generation of oscillatory and synchronous network activity. The specific role of various GABAergic subpopulations, however, has remained elusive. This is in part attributable to the scarcity of certain GABAergic neurons and the difficulty of identifying them in slices obtained from brain regions in which anatomical structures are not readily recognizable in the live preparation. To facilitate the functional analysis of GABAergic interneurons, we generated transgenic mice in which the enhanced green fluorescent protein (EGFP) was specifically expressed in parvalbumin-positive neurons. The high fidelity of expression obtained using bacterial artificial chromosome transgenes resulted in EGFP-labeled neurons in nearly all brain regions known to contain parvalbumin-expressing neurons. Immunocytochemical analysis showed that EGFP expression was primarily restricted to parvalbumin-positive cells. In addition to cell body labeling, EGFP expression was high enough in many neurons to enable the visualization of dendritic structures. With the help of these mice, we investigated the presence of electrical coupling between parvalbumin-positive cells in brain slices obtained from young and adult animals. In dentate gyrus basket cells, electrical coupling was found in slices from young [postnatal day 14 (P14)] and adult (P28 and P42) animals, but both strength and incidence of coupling decreased during development. However, electrical coupling between parvalbumin-positive multipolar cells in layer II/III of the neocortex remains unaltered during development. Yet another developmental profile of electrical coupling was found between layer II/III parvalbumin-positive cells and excitatory principal cells. Between these neurons, electrical coupling was found at P14 but not at P28. The results indicate that the presence and strength of electrical coupling is developmentally regulated with respect to brain area and cell type.

In vitro networks: cortical mechanisms of anaesthetic action

In vitro networks: cortical mechanisms of anaesthetic action

Muscarinic Induction of Hippocampal Gamma Oscillations Requires Coupling of the M1 Receptor to Two Mixed Cation Currents

Oscillatory network activity at γ frequencies is assumed to be of major importance in cortical information processing. Whereas the synaptic mechanisms of γ oscillations have been studied in detail, the ionic currents involved at the cellular level remain to be elucidated. Here we show that in vitro γ oscillations induced by muscarine require activation of M1 receptors on hippocampal CA3 pyramidal neurons and are absent in M1 receptor-deficient mice. M1 receptor activation depolarizes pyramidal neurons by increasing the mixed Na +/K + current I h and the Ca 2+-dependent nonspecific cation current I cat, but not by modulation of I M. Our data provide important insight into the molecular basis of γ oscillations by unequivocally establishing a novel role for muscarinic modulation of I h and I cat in rhythmic network activity.

Axonal gap junctions between principal neurons: a novel source of network oscillations, and perhaps epileptogenesis.

We hypothesized in 1998 that gap junctions might be located between the axons of principal hippocampal neurons, based on the shape of spikelets (fast prepotentials), occurring during gap junction-mediated very fast (to approximately 200 Hz) network oscillations in vitro. More recent electrophysiological, pharmacological and dye-coupling data indicate that axonal gap junctions exist; so far, they appear to be located about 100 microm from the soma, in CA1 pyramidal neurons. Computer modeling and theory predict that axonal gap junctions can lead to very fast network oscillations under three conditions: a) there are spontaneous axonal action potentials; b) the number of gap junctions in the network is neither too low (not less than to approximately 1.5 per cell on average), nor too high (not more than to approximately 3 per cell on average); c) action potentials can cross from axon to axon via gap junctions. Simulated oscillations resemble biological ones, but condition (c) remains to be demonstrated directly. Axonal network oscillations can, in turn, induce oscillatory activity in larger neuronal networks, by a variety of mechanisms. Axonal networks appear to underlie in vivo ripples (to approximately 200 Hz field potential oscillations superimposed on physiological sharp waves), to drive gamma (30-70 Hz) oscillations that appear in the presence of carbachol, and to initiate certain types of ictal discharge. If axonal gap junctions are important for seizure initiation in humans, there could be practical consequences for antiepileptic therapy: at least one gap junction-blocking compound, carbenoxolone, is already in clinical use (for treatment of ulcer disease), and it crosses the blood-brain barrier.

Synchronous Oscillatory Activity in Immature Cortical Network Is Driven by GABAergic Preplate Neurons

Neurons dissociated from embryonic cerebral rat cortex form a differentiated network of synaptic connections and develop synchronous oscillatory network activity with the beginning of the second week in culture. During an initial phase lasting 3-4 d, synchronous calcium transients can be blocked completely by either CNQX or bicuculline, showing that both glutamatergic and GABAergic neurons are required for the generation of this form of activity. By manipulating dissociation and growth conditions, cultures containing different populations of GABAergic neurons were obtained. These cultures revealed that a distinct population of large GABAergic neurons is a key element in the generation of synchronous oscillatory network activity. A minimal number of two large GABAergic neurons per square millimeter are required for the occurrence of synchronous activity. Changes in the density of all other types of GABAergic or non-GABAergic neurons has no influence on the synchronous activity. Electron microscopic analysis shows that the large GABAergic neurons form an interconnected network. Exceptionally high somatodendritic innervation and extended axonal arborization enable these neurons to collect electric network activity and to distribute it effectively throughout the neuronal network. Additional experiments indicated that most neurons developing in culture to large GABAergic neurons are derived from the primordial plexiform layer and reside in the subplate at the time of birth. We suggest that they function as an integrating element that synchronizes neuronal activity during early cortical development by collecting incoming extrinsic and intrinsic signals and distributing them effectively throughout the developing cortical plate.

Entorhinal cortex projection cells to the hippocampal formation in vitro

Retrogradely labeled cells in superficial and deep layers of the entorhinal cortex (EC) were analyzed following application of the fluorescent tracer rhodamine-dextran-amine in different sites of the hippocampal formation in a slice preparation. The results demonstrate a strong projection from layer IV/V to the dentate gyrus, that is in slices significantly stronger than that from layer II. In deep layers a large number of multipolar cells were found which were only labeled by dye application to the subiculum. Patch-clamp recordings from these cells revealed intrinsic low threshold membrane potential oscillations, suggesting their possible contribution to oscillatory network activity of the EC and subiculum.

EEG Frequency and Phase Coupling during Human Information Processing

Neuronal activity during information processing is represented by oscillations within local or widespread neuronal networks. These oscillations may be recorded by the EEG (electroencephalogram). The oscillatory interaction between neuronal ensembles may be at one single frequency or at different frequencies due to non-linear coupling. The investigation of momentary coherence and phase enables the examination of synchronized oscillatory network activity during fast-changing cognitive processes. On this basis information transfer from occipital areas towards frontal areas could be described during processing of visual presented words. Non-linear phase coupling between oscillations with different frequencies during memory processing was detected by means of cross-bicoherence.

Identification of biological signal sources for circadian and cardiac cycle rhythms using BP neural networks

Biological oscillatory activity in neural networks has been intensively studied over the past years. Neuronal oscillations are the basis of many different behavioral patterns and sensory mechanism. Understanding the dynamic properties of these mechanisms is useful for analyses of biological functions and medical diagnoses. The dynamic characteristics of wake‐sleep circadian rhythms and ECG’s cardiac cycle data measured for normal subjects are identified here, using MA‐BP neural network model. It was found that dynamics of regular components can be captured by the model. The captured dynamics are kept in a steady state for some periods. The order of the MA neural network was suppressively controlled by the first 2∼3 orders. Hence it may be useful for medical diagnoses of circadian rhythms and heart related diseases.

Précis of Neural organization: structure, function, and dynamics.

NEURAL ORGANIZATION: Structure, function, and dynamics shows how theory and experiment can supplement each other in an integrated, evolving account of the brain's structure, function, and dynamics. (1) STRUCTURE: Studies of brain function and dynamics build on and contribute to an understanding of many brain regions, the neural circuits that constitute them, and their spatial relations. We emphasize Szentágothai's modular architectonics principle, but also stress the importance of the microcomplexes of cerebellar circuitry and the lamellae of hippocampus. (2) FUNCTION: Control of eye movements, reaching and grasping, cognitive maps, and the roles of vision receive a functional decomposition in terms of schemas. Hypotheses as to how each schema is implemented through the interaction of specific brain regions provide the basis for modeling the overall function by neural networks constrained by neural data. Synthetic PET integrates modeling of primate circuitry with data from human brain imaging. (3) DYNAMICS: Dynamic system theory analyzes spatiotemporal neural phenomena, such as oscillatory and chaotic activity in both single neurons and (often synchronized) neural networks, the self-organizing development and plasticity of ordered neural structures, and learning and memory phenomena associated with synaptic modification. Rhythm generation involves multiple levels of analysis, from intrinsic cellular processes to loops involving multiple brain regions. A variety of rhythms are related to memory functions. The Précis presents a multifaceted case study of the hippocampus. We conclude with the claim that language and other cognitive processes can be fruitfully studied within the framework of neural organization that the authors have charted with John Szentágothai.

Muscarinic control of intracortical connections to layer II in rat entorhinal cortex slice

The cholinergic system is critically involved in oscillatory network activity and synaptic plasticity in the entorhinal cortex (EC) hippocampal formation. Here we demonstrate robust inhibition of field potentials in layer II of the medial EC evoked by stimulation in the deep EC or in the lateral layer II by carbachol (CCh, 0.1–100 μM, K D ~1 μM). This effect appears not to be mediated by suppression of presynaptic Ca 2+-signals since paired pulse facilitation was increased by CCh. Blockade of the effect by the muscarinic antagonists atropine and pirenzepine demonstrates mediation by muscarinic receptors, most likely of the M1 subtype. The effect is characterized by absence of desensitization and should be important for laminar shaping of oscillatory activity and synaptic plasticity during acetylcholine-dependent theta-rhythmic activity.

Cholinergic activation and tonic excitation induce persistent gamma oscillations in mouse somatosensory cortex in vitro.

1. Concomitant application of the cholinergic agonist carbachol and nanomolar doses of kainate can elicit persistent gamma frequency oscillations in all layers of the mouse somatosensory cortex in vitro. Receptor pharmacology with bath-applied antagonists indicated that oscillatory network activity depended crucially on the participation of cholinergic muscarinic, (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate and GABAA receptors. 2. The timing of action potentials and the occurrence of excitatory as well as inhibitory postsynaptic events was highly correlated with the phasic change of extracellularly recorded population activity. Firing probability was lowest during the peak negativity of IPSPs and gradually increased during their ensuing decay. In conjunction with the effect of a barbiturate to decrease the frequency of gamma oscillations, this suggests a crucial role of IPSPs in phasing the suprathreshold activity of principal neurons. 3. At nearby (< 1 mm) sites contained within any given cortical layer, oscillatory extra- and intracellular activity was highly synchronous with no apparent phase lag. However, interlaminar mapping experiments demonstrated a phase reversal of both extra- and intracellularly recorded activity near the lower border of thalamo-recipient layer 4, thus corroborating findings that have been obtained in vivo. 4. In conclusion, a modest increase of tonic excitatory drive in conjunction with the activation of cholinergic muscarinic receptors can elicit persistent gamma frequency network oscillations in the rodent somatosensory cortex. These findings (re)emphasize the role of the cholinergic ascending system in the cortical processing of sensory information.

O-2-23 - Expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) in meningiomas and associated peritumoral edema

Deep brain stimulation (DBS) was first used to treat essential tremor and the movement disorders associated with Parkinson disease. Its success led to its consideration as treatment for a wide variety of applications, including other neurologic as well as psychiatric and cognitive impairments. Extensive research conducted over the past 20 years has attempted to explain the as-yet uncertain mechanisms of DBS, with a focus on its effects on neuronal and astrocytic activity at the cellular, regional, and network level within the basal ganglia thalamocortical circuitry. Based on experimental evidence and theoretical considerations, five potentially co-occurring mechanisms have been proposed. DBS may produce local changes in the stimulated brain nuclei, as well as distal changes in efferent outputs and target nuclei.These theories of mechanism may not be exclusionary. Determining the degree to which some or all of these cellular and circuitry mechanisms account for the therapeutic efficacy as well as the potential adverse effects of DBS has been an important matter of debate. A review of the literature suggests that DBS mechanisms of action may be too complex to be supported by a single hypothesis, and they cannot be reduced to a simple question of inactivation or inhibition of neuronal activity and neurotransmission. This review summarizes each of these theories and advances in the understanding of the action of DBS, particularly as they relate to the modulation of neuronal spike generation, oscillatory network activity, and enhanced neurotransmission in the basal ganglia–thalamocortical circuit.

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<h3>SUMMARY</h3> Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed cortical organoids that spontaneously display periodic and regular oscillatory network events that are dependent on glutamatergic and GABAergic signaling. These nested oscillations exhibit cross-frequency coupling, proposed to coordinate neuronal computation and communication. As evidence of potential network maturation, oscillatory activity subsequently transitioned to more spatiotemporally irregular patterns, capturing features observed in preterm human electroencephalography (EEG). These results show that the development of structured network activity in the human neocortex may follow stable genetic programming, even in the absence of external or subcortical inputs. Our approach provides novel opportunities for investigating and manipulating the role of network activity in the developing human cortex. <h3>HIGHLIGHTS</h3> Early development of human functional neural networks and oscillatory activity can be modeled <i>in vitro</i>. Cortical organoids exhibit phase-amplitude coupling between delta oscillation (2 Hz) and high-frequency activity (100-400 Hz) during network-synchronous events. Differential role of glutamate and GABA in initiating and maintaining oscillatory network activity. Developmental impairment of MECP2-KO cortical organoids impacts the emergence of oscillatory activity. Cortical organoid network electrophysiological signatures correlate with human preterm neonatal EEG features. <h3>eTOC</h3> Brain oscillations are a candidate mechanism for how neural populations are temporally organized to instantiate cognition and behavior. Cortical organoids initially exhibit periodic and highly regular nested oscillatory network events that eventually transition to more spatiotemporally complex activity, capturing features of late-stage preterm infant electroencephalography. Functional neural circuitry in cortical organoids exhibits emergence and development of oscillatory network dynamics similar to those found in the developing human brain.