Dynamical ventral tegmental area circuit mechanisms of alcohol‐dependent dopamine release
A large body of data has identified numerous molecular targets through which ethanol (EtOH) acts on brain circuits. Yet how these multiple mechanisms interact to result in dysregulated dopamine (DA) release under the influence of alcohol in vivo remains unclear. In this manuscript, we delineate potential circuit‐level mechanisms responsible for EtOH‐dependent dysregulation of DA release from the ventral tegmental area (VTA) into its projection areas. For this purpose, we constructed a circuit model of the VTA that integrates realistic Glutamatergic (Glu) inputs and reproduces DA release observed experimentally. We modelled the concentration‐dependent effects of EtOH on its principal VTA targets. We calibrated the model to reproduce the inverted U‐shape dose dependence of DA neuron activity on EtOH concentration. The model suggests a primary role of EtOH‐induced boost in the Ih and AMPA currents in the DA firing‐rate/bursting increase. This is counteracted by potentiated GABA transmission that decreases DA neuron activity at higher EtOH concentrations. Thus, the model connects well‐established in vitro pharmacological EtOH targets with its in vivo influence on neuronal activity. Furthermore, we predict that increases in VTA activity produced by moderate EtOH doses require partial synchrony and relatively low rates of the Glu afferents. We propose that the increased frequency of transient (phasic) DA peaks evoked by EtOH results from synchronous population bursts in VTA DA neurons. Our model predicts that the impact of acute ETOH on dopamine release is critically shaped by the structure of the cortical inputs to the VTA.
In this paper, we study the dynamics of a quadratic integrate-and-fire neuron, spiking in the gamma (30-100 Hz) range, coupled to a delta/theta frequency (1-8 Hz) neural oscillator. Using analytical and semianalytical methods, we were able to derive characteristic spiking times for the system in two distinct regimes (depending on parameter values): one regime where the gamma neuron is intrinsically oscillating in the absence of theta input, and a second one in which gamma spiking is directly gated by theta input, i.e., windows of gamma activity alternate with silence periods depending on the underlying theta phase. In the former case, we transform the equations such that the system becomes analogous to the Mathieu differential equation. By solving this equation, we can compute numerically the time to the first gamma spike, and then use singular perturbation theory to find successive spike times. On the other hand, in the excitable condition, we make direct use of singular perturbation theory to obtain an approximation of the time to first gamma spike, and then extend the result to calculate ensuing gamma spikes in a recursive fashion. We thereby give explicit formulas for the onset and offset of gamma spike burst during a theta cycle, and provide an estimation of the total number of spikes per theta cycle both for excitable and oscillator regimes.
Working memory (WM) requires selective information gating, active information maintenance, and rapid active updating. Hence performing a WM task needs rapid and controlled transitions between neural persistent activity and the resting state. We propose that changes in correlations in neural activity provides a mechanism for the required WM operations. As a proof of principle, we implement sustained activity and WM in recurrently coupled spiking networks with neurons receiving excitatory random background activity where background correlations are induced by a common noise source. We first characterize how the level of background correlations controls the stability of the persistent state. With sufficiently high correlations, the sustained state becomes practically unstable, so it cannot be initiated by a transient stimulus. We exploit this in WM models implementing the delay match to sample task by modulating flexibly in time the correlation level at different phases of the task. The modulation sets the network in different working regimes: more prompt to gate in a signal or clear the memory. We examine how the correlations affect the ability of the network to perform the task when distractors are present. We show that in a winner-take-all version of the model, where two populations cross-inhibit, correlations make the distractor blocking robust. In a version of the mode where no cross inhibition is present, we show that appropriate modulation of correlation levels is sufficient to also block the distractor access while leaving the relevant memory trace in tact. The findings presented in this manuscript can form the basis for a new paradigm about how correlations are flexibly controlled by the cortical circuits to execute WM operations.
The Book Of Alexander Alexandrovich Zinoviev "Veselie Rusi. Scenes from the life of Russian Drunks", published in Milan in the distant perestroika 1989, is dedicated to the ordinary Soviet drunkard. The book, in addition to poems, contains 30 cartoons covering the life path from birth to death. But the product is not so much about the drunk, but about Soviet life in General. Zinoviev in the photographic image the underside of Soviet life. With his usual irony he sees in drunkenness the way "not to see the abomination being". The author proposes a new formula of Soviet reality: "Soviet power + party = drinking". On imposed on top of the principles and rules of the hostel drinking the population answered in the language of the "culture of laughter." This language is very subtly captured and decoded Alexander, turning his work into an illustrated "encyclopedia" of Soviet reality in General, and drunkenness in particular.
Cognitive effort leads to a seeming cacophony of brain oscillations. For example, during tasks engaging working memory (WM), specific oscillatory frequency bands modulate in space and time. Despite ample data correlating such modulation to task performance, a mechanistic explanation remains elusive. We propose that flexible control of neural oscillations provides a unified mechanism for the rapid and controlled transitions between the computational operations required by WM. We show in a spiking network model that modulating the input oscillation frequency sets the network in different operating modes: rapid memory access and load is enabled by the beta-gamma oscillations, maintaining a memory while ignoring distractors by the theta, rapid memory clearance by the alpha. The various frequency bands determine the dynamic gating regimes enabling the necessary operations for WM, whose succession explains the need for the complex oscillatory brain dynamics during effortful cognition.
The distractive effects on attentional task performance in different paradigms are analyzed in this paper. I demonstrate how distractors may negatively affect (interference effect), positively (redundancy effect) or neutrally (null effect). Distractor effects described in literature are classified in accordance with their hypothetical source. The general rule of the theory is also introduced. It contains the formal prediction of the particular distractor effect, based on entropy and redundancy measures from the mathematical theory of communication (Shannon, 1948). Single- vs dual-process frameworks are considered for hypothetical mechanisms which underpin the distractor effects. Distractor profiles (DPs) are also introduced for the formalization and simple visualization of experimental data concerning the distractor effects. Typical shapes of DPs and their interpretations are discussed with examples from three frequently cited experiments. Finally, the paper introduces hierarchical hypothesis that states the level-fashion modulating interrelations between distractor effects of different classes.
This article describes the expierence of studying factors influencing the social well-being of educational migrants as mesured by means of a psychological well-being scale (A. Perrudet-Badoux, G.A. Mendelsohn, J.Chiche, 1988) previously adapted for Russian by M.V. Sokolova. A statistical analysis of the scale's reliability is performed. Trends in dynamics of subjective well-being are indentified on the basis the correlations analysis between the condbtbions of adaptation and its success rate, and potential mechanisms for developing subjective well-being among student migrants living in student hostels are described. Particular attention is paid to commuting as a factor of adaptation.
Hypoxia of trophoblast cells is an important regulator of normal development of the placenta. However, some pathological states associated with hypoxia, e.g. preeclampsia, impair the functions of placental cells. Oxyquinoline derivative inhibits HIF-prolyl hydroxylase by stabilizing HIF-1 transcription complex, thus modeling cell response to hypoxia. In human choriocarcinoma cells BeWo b30 (trophoblast model), oxyquinoline increased the expression of a core hypoxia response genes along with up-regulation of NOS3, PDK1, and BNIP3 genes and down-regulation of the PPARGC1B gene. These changes in the expression profile attest to activation of the metabolic cell reprogramming mechanisms aimed at reducing oxygen consumption by enabling the switch from aerobic to anaerobic glucose metabolism and the respective decrease in number of mitochondria. The possibility of practical use of the therapeutic properties of oxyquinoline derivatives is discussed.
This article is talking about state management and cultural policy, their nature and content in term of the new tendency - development of postindustrial society. It mentioned here, that at the moment cultural policy is the base of regional political activity and that regions can get strong competitive advantage if they are able to implement cultural policy successfully. All these trends can produce elements of new economic development.