Stimulus statistics shape oscillations in nonlinear recurrent neural networks.

Rhythmic activity plays a central role in neural computations and brain functions ranging from homeostasis to attention, as well as in neurological and neuropsychiatric disorders. Despite this pervasiveness, little is known about the mechanisms whereby the frequency and power of oscillatory activity are modulated, and how they reflect the inputs received by neurons. Numerous studies have reported input-dependent fluctuations in peak frequency and power (as well as couplings across these features). However, it remains unresolved what mediates these spectral shifts among neural populations. Extending previous findings regarding stochastic nonlinear systems and experimental observations, we provide analytical insights regarding oscillatory responses of neural populations to stimulation from either endogenous or exogenous origins. Using a deceptively simple yet sparse and randomly connected network of neurons, we show how spiking inputs can reliably modulate the peak frequency and power expressed by synchronous neural populations without any changes in circuitry. Our results reveal that a generic, non-nonlinear and input-induced mechanism can robustly mediate these spectral fluctuations, and thus provide a framework in which inputs to the neurons bidirectionally regulate both the frequency and power expressed by synchronous populations. Theoretical and computational analysis of the ensuing spectral fluctuations was found to reflect the underlying dynamics of the input stimuli driving the neurons. Our results provide insights regarding a generic mechanism supporting spectral transitions observed across cortical networks and spanning multiple frequency bands.

Age-related differences on event-related potentials and brain rhythm oscillations during working memory activation.

Previous functional imaging studies have pointed to the compensatory recruitment of cortical circuits in old age in order to counterbalance the loss of neural efficiency and preserve cognitive performance. Recent electroencephalographic (EEG) analyses reported age-related deficits in the amplitude of an early positive-negative working memory (PN(wm)) component as well as changes in working memory (WM)-load related brain oscillations during the successful performance of the n-back task. To explore the age-related differences of EEG activation in the face of increasing WM demands, we assessed the PN(wm) component area, parietal alpha event-related synchronization (ERS) as well as frontal theta ERS in 32 young and 32 elderly healthy individuals who successfully performed a highly WM demanding 3-back task. PN(wm) area increased with higher memory loads (3- and 2-back > 0-back tasks) in younger subjects. Older subjects reached the maximal values for this EEG parameter during the less WM demanding 0-back task. They showed a rapid development of an alpha ERS that reached its maximal amplitude at around 800 ms after stimulus onset. In younger subjects, the late alpha ERS occurred between 1,200 and 2,000 ms and its amplitude was significantly higher compared with elders. Frontal theta ERS culmination peak decreased in a task-independent manner in older compared with younger cases. Only in younger individuals, there was a significant decrease in the phasic frontal theta ERS amplitude in the 2- and 3-back tasks compared with the detection and 0-back tasks. These observations suggest that older adults display a rapid mobilization of their neural generators within the parietal cortex to manage very low demanding WM tasks. Moreover, they are less able to activate frontal theta generators during attentional tasks compared with younger persons.

Cdc42 oscillations in yeasts.

A fundamental problem in cell biology is how cells define one or several discrete sites of polarity. Through mechanisms involving positive and negative feedback, the small Rho-family guanosine triphosphatase Cdc42 breaks symmetry in round budding yeast cells to define a single site of polarized cell growth. However, it is not clear how cells can define multiple sites of polarization concurrently. We discuss a study in which rod-shaped fission yeast cells, which naturally polarize growth at their two cell ends, exhibited oscillations of Cdc42 activity between these sites. We compare these findings with similar oscillatory behavior of Cdc42 detected in budding yeast cells and discuss the possible mechanism and functional outputs of these oscillations.

Early glutathione deficit impairs parvalbumin expression in gaba interneurons and kainate-induced gamma oscillations

An increased oxidative stress and alteration of the antioxidant systems have been observed in schizophrenia. Glutathione (GSH), a major redox regulator, is decreased in patients' cerebrospinal fluid, prefrontal cortex in vivo and striatum post-mortem tissue. Most importantly, there is genetic and functional evidence for the implication of the gene of the glutamate cysteine ligase (GCL) catalytic subunit, the key GSH-synthesizing enzyme. We have developed animal models for a GSH deficit to study the consequences of such deficit on the brain development. A GSH deficit combined with elevated dopamine (DA) during development leads to reduced parvalbumin (PV) expression in a subclass of GABA interneurons in rat anterior cingulate cortex (ACC). Similar changes are observed in postmortem brain tissue of schizophrenic patients. GSH dysregulation increases vulnerability to oxidative stress, that in turn could lead to cortical circuit anomalies in the schizophrenic brain. In the present study, we use a GCL modulatory subunit (GCLM) knock-out (KO) mouse model that presents up to 80% decreased brain GSH levels. During postnatal development, a subgroup of animals from each genotype is exposed to elevated oxidative stress induced by treatment with the DA reuptake inhibitor GBR12909. Results reveal a significant genotype-specific delay International Congress on Schizophrenia Research 136 10. 10. Neuroanatomy, Animal Downloaded from http://schizophreniabulletin.oxfordjournals.org at Bibliotheque Cantonale et Universitaire on June 18, 2010 in cortical PV expression at postnatal day P10 in GCLM-KO mice, as compared to wild-type. This effect seems to be further exaggerated in animals treated with GBR12909 from P5 to P10. At P20, PV expression is no longer significantly reduced in GCLM-KO ACC without GBR but is reduced if GBR is applied from P10 to P20. However, our result show that GCLM-KO mice exhibit increased oxidative stress, cortical altered myelin development as shown by MBP marker, and more specifically impairment of the peri-neuronal net known to modulate PV connectivity. In addition, we also observe a reduced PV expression in the ventro-temporal hippocampus of adult GCLM-KO mice, suggesting that anomalies of the PV interneurons prevail at least in some brain regions throughout the adulthood. Interestingly, the power of kainate-induced gamma oscillations, known to be dependent on proper activation of PV interneuron's, is also lower in hippocampal slices of adult GCLM KO mice. These results suggest that the PV positive GABA interneurons is particularly vulnerable to increased oxidative stress

Redox dysregulation affects the ventral but not dorsal hippocampus: impairment of parvalbumin neurons, gamma oscillations, and related behaviors.

Elevated oxidative stress and alteration in antioxidant systems, including glutathione (GSH) decrease, are observed in schizophrenia. Genetic and functional data indicate that impaired GSH synthesis represents a susceptibility factor for the disorder. Here, we show that a genetically compromised GSH synthesis affects the morphological and functional integrity of hippocampal parvalbumin-immunoreactive (PV-IR) interneurons, known to be affected in schizophrenia. A GSH deficit causes a selective decrease of PV-IR interneurons in CA3 and dendate gyrus (DG) of the ventral but not dorsal hippocampus and a concomitant reduction of beta/gamma oscillations. Impairment of PV-IR interneurons emerges at the end of adolescence/early adulthood as oxidative stress increases or cumulates selectively in CA3 and DG of the ventral hippocampus. Such redox dysregulation alters stress and emotion-related behaviors but leaves spatial abilities intact, indicating functional disruption of the ventral but not dorsal hippocampus. Thus, a GSH deficit affects PV-IR interneuron's integrity and neuronal synchrony in a region- and time-specific manner, leading to behavioral phenotypes related to psychiatric disorders.

Oscillations, phase-of-firing coding, and spike timing-dependent plasticity: an efficient learning scheme

Recent experiments have established that information can be encoded in the spike times of neurons relative to the phase of a background oscillation in the local field potential—a phenomenon referred to as “phase-of-firing coding” (PoFC). These firing phase preferences could result from combining an oscillation in the input current with a stimulus-dependent static component that would produce the variations in preferred phase, but it remains unclear whether these phases are an epiphenomenon or really affect neuronal interactions—only then could they have a functional role. Here we show that PoFC has a major impact on downstream learning and decoding with the now well established spike timing-dependent plasticity (STDP). To be precise, we demonstrate with simulations how a single neuron equipped with STDP robustly detects a pattern of input currents automatically encoded in the phases of a subset of its afferents, and repeating at random intervals. Remarkably, learning is possible even when only a small fraction of the afferents (~10%) exhibits PoFC. The ability of STDP to detect repeating patterns had been noted before in continuous activity, but it turns out that oscillations greatly facilitate learning. A benchmark with more conventional rate-based codes demonstrates the superiority of oscillations and PoFC for both STDP-based learning and the speed of decoding: the oscillation partially formats the input spike times, so that they mainly depend on the current input currents, and can be efficiently learned by STDP and then recognized in just one oscillation cycle. This suggests a major functional role for oscillatory brain activity that has been widely reported experimentally.

Pre-stimulus beta oscillations within left posterior sylvian regions impact auditory temporal order judgment accuracy.

Both neural and behavioral responses to stimuli are influenced by the state of the brain immediately preceding their presentation, notably by pre-stimulus oscillatory activity. Using frequency analysis of high-density electroencephalogram coupled with source estimations, the present study investigated the role of pre-stimulus oscillatory activity in auditory spatial temporal order judgments (TOJ). Oscillations within the beta range (i.e. 18-23Hz) were significantly stronger before accurate than inaccurate TOJ trials. Distributed source estimations identified bilateral posterior sylvian regions as the principal contributors to pre-stimulus beta oscillations. Activity within the left posterior sylvian region was significantly stronger before accurate than inaccurate TOJ trials. We discuss our results in terms of a modulation of sensory gating mechanisms mediated by beta activity.

Blood-Borne Circadian Signal Stimulates Daily Oscillations in Actin Dynamics and SRF Activity.

In peripheral tissues circadian gene expression can be driven either by local oscillators or by cyclic systemic cues controlled by the master clock in the brain's suprachiasmatic nucleus. In the latter case, systemic signals can activate immediate early transcription factors (IETFs) and thereby control rhythmic transcription. In order to identify IETFs induced by diurnal blood-borne signals, we developed an unbiased experimental strategy, dubbed Synthetic TAndem Repeat PROMoter (STAR-PROM) screening. This technique relies on the observation that most transcription factor binding sites exist at a relatively high frequency in random DNA sequences. Using STAR-PROM we identified serum response factor (SRF) as an IETF responding to oscillating signaling proteins present in human and rodent sera. Our data suggest that in mouse liver SRF is regulated via dramatic diurnal changes of actin dynamics, leading to the rhythmic translocation of the SRF coactivator Myocardin-related transcription factor-B (MRTF-B) into the nucleus.

Atypical coordination of cortical oscillations in response to speech in autism.

Subjects with autism often show language difficulties, but it is unclear how they relate to neurophysiological anomalies of cortical speech processing. We used combined EEG and fMRI in 13 subjects with autism and 13 control participants and show that in autism, gamma and theta cortical activity do not engage synergistically in response to speech. Theta activity in left auditory cortex fails to track speech modulations, and to down-regulate gamma oscillations in the group with autism. This deficit predicts the severity of both verbal impairment and autism symptoms in the affected sample. Finally, we found that oscillation-based connectivity between auditory and other language cortices is altered in autism. These results suggest that the verbal disorder in autism could be associated with an altered balance of slow and fast auditory oscillations, and that this anomaly could compromise the mapping between sensory input and higher-level cognitive representations.

Langues et identités culturelles: oscillations de l'école du monolinguisme au plurilinguisme et des discours aux pratiques.

Pourquoi traiter de l'école pour aborder le rapport entre langue et culture ? Car, dans mon parcours personnel, l'institution scolaire a tenu un rôle prédominant dans la construction du lien entre mes langues - l'italien et le français - et mes appartenances culturelles. Ainsi, la première partie du mémoire porte sur cette histoire-là d'une part, et sur l'élaboration du travail de recherche de l'autre. La deuxième et la troisième partie du mémoire affrontent les oscillations de l'école quant à la question linguistique. Le terme école comprend ici tout ce qui touche, conceptuellement ou pragmatiquement, au monde scolaire. En effet, les discours sur l'école et les pratiques au sein de l'école sont les deux facettes d'une même médaille. Plus précisément, la deuxième partie expose les rhétoriques émanant des sciences humaines d'un côté, et des discours politiques de l'autre. Nous verrons comment ces deux sphères sont étroitement liées. D'une même voix, elles affirment le lien entre la langue et l'identité culturelle et exhortent l'institution scolaire à la valorisation du multilinguisme. Comme annoncé, la troisième partie constitue un retour au singulier et entre dans la pratique de l'école. A travers les entretiens réalisés avec des enseignants de l'école vaudoise, il s'agit d'appréhender le lien entre les discours et les pratiques, l'universel et le particulier. Nous constaterons qu'à ce niveau-là, les credo du monolinguisme et du multilinguisme combattent encore l'un contre l'autre. Expliciter le sous-titre du mémoire permet de réduire les malentendus. Celui-ci annonce deux types d'oscillations, étroitement articulées l'une à l'autre. Premièrement, les oscillations du monolinguisme au plurilinguisme observables dans deux dimensions. Une diachronique - qui n'est pas traitée dans ce travail - mettrait en lumière le passage d'une conception strictement monolingue de l'école à une conception plurilingue qui se diffuse depuis quelques années. La dimension synchronique, retenue dans ce mémoire, révèle comment, au sein du corps enseignant vaudois d'aujourd'hui, la perception monolingue des uns résiste aux assauts du paradigme plurilingue des autres. Deuxièmement, les oscillations de l'école prise entre les discours et les pratiques. Tantôt dans un rapport de force, tantôt dans une réciprocité créatrice, ces deux pôles négocient constamment les conditions d'existence de l'école. L'actualité de l'école vaudoise, avec la réintroduction des notes au niveau secondaire à la rentrée scolaire d'août 2005, est un exemple concret de cette oscillation de l'institution scolaire qui résulte de la négociation entre les discours et les pratiques.