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Hamaguchi, Kosuke, Alexa Riehle, and Nicolas Brunel. "Estimating Network Parameters From Combined Dynamics of Firing Rate and Irregularity of Single Neurons." Journal of Neurophysiology 105, no. 1 (January 2011): 487–500. http://dx.doi.org/10.1152/jn.00858.2009.
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High firing irregularity is a hallmark of cortical neurons in vivo, and modeling studies suggest a balance of excitation and inhibition is necessary to explain this high irregularity. Such a balance must be generated, at least partly, from local interconnected networks of excitatory and inhibitory neurons, but the details of the local network structure are largely unknown. The dynamics of the neural activity depends on the local network structure; this in turn suggests the possibility of estimating network structure from the dynamics of the firing statistics. Here we report a new method to estimate properties of the local cortical network from the instantaneous firing rate and irregularity (CV2) under the assumption that recorded neurons are a part of a randomly connected sparse network. The firing irregularity, measured in monkey motor cortex, exhibits two features; many neurons show relatively stable firing irregularity in time and across different task conditions; the time-averaged CV2 is widely distributed from quasi-regular to irregular (CV2 = 0.3–1.0). For each recorded neuron, we estimate the three parameters of a local network [balance of local excitation-inhibition, number of recurrent connections per neuron, and excitatory postsynaptic potential (EPSP) size] that best describe the dynamics of the measured firing rates and irregularities. Our analysis shows that optimal parameter sets form a two-dimensional manifold in the three-dimensional parameter space that is confined for most of the neurons to the inhibition-dominated region. High irregularity neurons tend to be more strongly connected to the local network, either in terms of larger EPSP and inhibitory PSP size or larger number of recurrent connections, compared with the low irregularity neurons, for a given excitatory/inhibitory balance. Incorporating either synaptic short-term depression or conductance-based synapses leads many low CV2 neurons to move to the excitation-dominated region as well as to an increase of EPSP size.
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Nguyen, Bao N., Allison M. McKendrick, and Algis J. Vingrys. "Abnormal inhibition-excitation imbalance in migraine." Cephalalgia 36, no. 1 (March 18, 2015): 5–14. http://dx.doi.org/10.1177/0333102415576725.
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Background People with migraine show increased surround suppression of perceived contrast, a perceptual analogue of centre-surround antagonistic interactions in visual cortex. A proposed mechanism is that cortical ‘hyperexcitability’ or ‘hyperresponsivity’, a prominent theory in the migraine literature, drives abnormal excitatory-inhibitory balance to give increased local inhibition. The purpose of this cross-sectional study was to determine whether cortical hyperresponsivity and excitatory-inhibitory imbalance manifests in the visual cortical response of migraine sufferers. Methods Interictal steady-state visual evoked potentials (VEPs) in response to 0 to 97% contrast were recorded in 30 migraine participants (15 without aura, 15 with aura) and 21 non-headache controls. Monotonicity indices were calculated to determine response saturation or supersaturation. Contrast gain was modelled with a modified saturating hyperbolic function to allow for variation in excitation and inhibition. Results A greater proportion of migraine participants (43%) than controls (14%) exhibited significant VEP supersaturation at high contrast, based on monotonicity index (chi-square, p = 0.028). Supersaturation was also evident by the trend for greater suppressive exponent values in migraine compared to control individuals (Mann-Whitney rank sum, p = 0.075). Conclusions Supersaturation in migraine is consistent with excess excitation (hyperresponsivity) driving increased network inhibition and provides support for excitatory-inhibitory imbalance as a pathophysiological disturbance in migraine.
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Wang, Jiang, Ruixue Han, Xilei Wei, Yingmei Qin, Haitao Yu, and Bin Deng. "Weak signal detection and propagation in diluted feed-forward neural network with recurrent excitation and inhibition." International Journal of Modern Physics B 30, no. 02 (January 20, 2016): 1550253. http://dx.doi.org/10.1142/s0217979215502537.
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Reliable signal propagation across distributed brain areas provides the basis for neural circuit function. Modeling studies on cortical circuits have shown that multilayered feed-forward networks (FFNs), if strongly and/or densely connected, can enable robust signal propagation. However, cortical networks are typically neither densely connected nor have strong synapses. This paper investigates under which conditions spiking activity can be propagated reliably across diluted FFNs. Extending previous works, we model each layer as a recurrent sub-network constituting both excitatory (E) and inhibitory (I) neurons and consider the effect of interactions between local excitation and inhibition on signal propagation. It is shown that elevation of cellular excitation–inhibition (EI) balance in the local sub-networks (layers) softens the requirement for dense/strong anatomical connections and thereby promotes weak signal propagation in weakly connected networks. By means of iterated maps, we show how elevated local excitability state compensates for the decreased gain of synchrony transfer function that is due to sparse long-range connectivity. Finally, we report that modulations of EI balance and background activity provide a mechanism for selectively gating and routing neural signal. Our results highlight the essential role of intrinsic network states in neural computation.
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Brunel, Nicolas, and Xiao-Jing Wang. "What Determines the Frequency of Fast Network Oscillations With Irregular Neural Discharges? I. Synaptic Dynamics and Excitation-Inhibition Balance." Journal of Neurophysiology 90, no. 1 (July 2003): 415–30. http://dx.doi.org/10.1152/jn.01095.2002.
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When the local field potential of a cortical network displays coherent fast oscillations (∼40-Hz gamma or ∼200-Hz sharp-wave ripples), the spike trains of constituent neurons are typically irregular and sparse. The dichotomy between rhythmic local field and stochastic spike trains presents a challenge to the theory of brain rhythms in the framework of coupled oscillators. Previous studies have shown that when noise is large and recurrent inhibition is strong, a coherent network rhythm can be generated while single neurons fire intermittently at low rates compared to the frequency of the oscillation. However, these studies used too simplified synaptic kinetics to allow quantitative predictions of the population rhythmic frequency. Here we show how to derive quantitatively the coherent oscillation frequency for a randomly connected network of leaky integrate-and-fire neurons with realistic synaptic parameters. In a noise-dominated interneuronal network, the oscillation frequency depends much more on the shortest synaptic time constants (delay and rise time) than on the longer synaptic decay time, and ∼200-Hz frequency can be realized with synaptic time constants taken from slice data. In a network composed of both interneurons and excitatory cells, the rhythmogenesis is a compromise between two scenarios: the fast purely interneuronal mechanism, and the slower feedback mechanism (relying on the excitatory-inhibitory loop). The properties of the rhythm are determined essentially by the ratio of time scales of excitatory and inhibitory currents and by the balance between the mean recurrent excitation and inhibition. Faster excitation than inhibition, or a higher excitation/inhibition ratio, favors the feedback loop and a much slower oscillation (typically in the gamma range).
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Harris, Kameron Decker, Tatiana Dashevskiy, Joshua Mendoza, Alfredo J. Garcia, Jan-Marino Ramirez, and Eric Shea-Brown. "Different roles for inhibition in the rhythm-generating respiratory network." Journal of Neurophysiology 118, no. 4 (October 1, 2017): 2070–88. http://dx.doi.org/10.1152/jn.00174.2017.
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Unraveling the interplay of excitation and inhibition within rhythm-generating networks remains a fundamental issue in neuroscience. We use a biophysical model to investigate the different roles of local and long-range inhibition in the respiratory network, a key component of which is the pre-Bötzinger complex inspiratory microcircuit. Increasing inhibition within the microcircuit results in a limited number of out-of-phase neurons before rhythmicity and synchrony degenerate. Thus unstructured local inhibition is destabilizing and cannot support the generation of more than one rhythm. A two-phase rhythm requires restructuring the network into two microcircuits coupled by long-range inhibition in the manner of a half-center. In this context, inhibition leads to greater stability of the two out-of-phase rhythms. We support our computational results with in vitro recordings from mouse pre-Bötzinger complex. Partial excitation block leads to increased rhythmic variability, but this recovers after blockade of inhibition. Our results support the idea that local inhibition in the pre-Bötzinger complex is present to allow for descending control of synchrony or robustness to adverse conditions like hypoxia. We conclude that the balance of inhibition and excitation determines the stability of rhythmogenesis, but with opposite roles within and between areas. These different inhibitory roles may apply to a variety of rhythmic behaviors that emerge in widespread pattern-generating circuits of the nervous system. NEW & NOTEWORTHY The roles of inhibition within the pre-Bötzinger complex (preBötC) are a matter of debate. Using a combination of modeling and experiment, we demonstrate that inhibition affects synchrony, period variability, and overall frequency of the preBötC and coupled rhythmogenic networks. This work expands our understanding of ubiquitous motor and cognitive oscillatory networks.
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Mariño, Jorge, James Schummers, David C. Lyon, Lars Schwabe, Oliver Beck, Peter Wiesing, Klaus Obermayer, and Mriganka Sur. "Invariant computations in local cortical networks with balanced excitation and inhibition." Nature Neuroscience 8, no. 2 (January 23, 2005): 194–201. http://dx.doi.org/10.1038/nn1391.
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Zheng, Ying, Jing Jing Luo, Sam Harris, Aneurin Kennerley, Jason Berwick, Steve A. Billings, and John Mayhew. "Balanced excitation and inhibition: Model based analysis of local field potentials." NeuroImage 63, no. 1 (October 2012): 81–94. http://dx.doi.org/10.1016/j.neuroimage.2012.06.040.
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Anticevic, Alan, and John Lisman. "How Can Global Alteration of Excitation/Inhibition Balance Lead to the Local Dysfunctions That Underlie Schizophrenia?" Biological Psychiatry 81, no. 10 (May 2017): 818–20. http://dx.doi.org/10.1016/j.biopsych.2016.12.006.
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Vattikonda, Anirudh, Bapi Raju Surampudi, Arpan Banerjee, Gustavo Deco, and Dipanjan Roy. "Does the regulation of local excitation–inhibition balance aid in recovery of functional connectivity? A computational account." NeuroImage 136 (August 2016): 57–67. http://dx.doi.org/10.1016/j.neuroimage.2016.05.002.
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Linster, Christiane, and Claudine Masson. "A Neural Model of Olfactory Sensory Memory in the Honeybee's Antennal Lobe." Neural Computation 8, no. 1 (January 1996): 94–114. http://dx.doi.org/10.1162/neco.1996.8.1.94.
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We present a neural model for olfactory sensory memory in the honeybee's antennal lobe. To investigate the neural mechanisms underlying odor discrimination and memorization, we exploit a variety of morphological, physiological, and behavioral data. The model allows us to study the computational capacities of the known neural circuitry, and to interpret under a new light experimental data on the cellular as well as on the neuronal assembly level. We propose a scheme for memorization of the neural activity pattern after stimulus offset by changing the local balance between excitation and inhibition. This modulation is achieved by changing the intrinsic parameters of local inhibitory neurons or synapses.
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Esser, Steve K., Sean Hill, and Giulio Tononi. "Breakdown of Effective Connectivity During Slow Wave Sleep: Investigating the Mechanism Underlying a Cortical Gate Using Large-Scale Modeling." Journal of Neurophysiology 102, no. 4 (October 2009): 2096–111. http://dx.doi.org/10.1152/jn.00059.2009.
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Effective connectivity between cortical areas decreases during slow wave sleep. This decline can be observed in the reduced interareal propagation of activity evoked either directly in cortex by transcranial magnetic stimulation (TMS) or by sensory stimulation. We present here a large-scale model of the thalamocortical system that is capable of reproducing these experimental observations. This model was constructed according to a large number of physiological and anatomical constraints and includes over 30,000 spiking neurons interconnected by more than 5 million synaptic connections and organized into three cortical areas. By simulating the different effects of arousal promoting neuromodulators, the model can produce a waking or a slow wave sleep-like mode. In this work, we also seek to explain why intercortical signal transmission decreases in slow wave sleep. The traditional explanation for reduced brain responses during this state, a thalamic gate, cannot account for the reduced propagation between cortical areas. Therefore we propose that a cortical gate is responsible for this diminished intercortical propagation. We used our model to test three candidate mechanisms that might produce a cortical gate during slow wave sleep: a propensity to enter a local down state following perturbation, which blocks the propagation of activity to other areas, increases in potassium channel conductance that reduce neuronal responsiveness, and a shift in the balance of synaptic excitation and inhibition toward inhibition, which decreases network responses to perturbation. Of these mechanisms, we find that only a shift in the balance of synaptic excitation and inhibition can account for the observed in vivo response to direct cortical perturbation as well as many features of spontaneous sleep.
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Busche, Marc Aurel, and Arthur Konnerth. "Impairments of neural circuit function in Alzheimer's disease." Philosophical Transactions of the Royal Society B: Biological Sciences 371, no. 1700 (August 5, 2016): 20150429. http://dx.doi.org/10.1098/rstb.2015.0429.
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An essential feature of Alzheimer's disease (AD) is the accumulation of amyloid-β (Aβ) peptides in the brain, many years to decades before the onset of overt cognitive symptoms. We suggest that during this very extended early phase of the disease, soluble Aβ oligomers and amyloid plaques alter the function of local neuronal circuits and large-scale networks by disrupting the balance of synaptic excitation and inhibition ( E / I balance) in the brain. The analysis of mouse models of AD revealed that an Aβ-induced change of the E / I balance caused hyperactivity in cortical and hippocampal neurons, a breakdown of slow-wave oscillations, as well as network hypersynchrony. Remarkably, hyperactivity of hippocampal neurons precedes amyloid plaque formation, suggesting that hyperactivity is one of the earliest dysfunctions in the pathophysiological cascade initiated by abnormal Aβ accumulation. Therapeutics that correct the E / I balance in early AD may prevent neuronal dysfunction, widespread cell loss and cognitive impairments associated with later stages of the disease. This article is part of the themed issue ‘Evolution brings Ca 2+ and ATP together to control life and death’.
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Renart, Alfonso, Rubén Moreno-Bote, Xiao-Jing Wang, and Néstor Parga. "Mean-Driven and Fluctuation-Driven Persistent Activity in Recurrent Networks." Neural Computation 19, no. 1 (January 2007): 1–46. http://dx.doi.org/10.1162/neco.2007.19.1.1.
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Spike trains from cortical neurons show a high degree of irregularity, with coefficients of variation (CV) of their interspike interval (ISI) distribution close to or higher than one. It has been suggested that this irregularity might be a reflection of a particular dynamical state of the local cortical circuit in which excitation and inhibition balance each other. In this “balanced” state, the mean current to the neurons is below threshold, and firing is driven by current fluctuations, resulting in irregular Poisson-like spike trains. Recent data show that the degree of irregularity in neuronal spike trains recorded during the delay period of working memory experiments is the same for both low-activity states of a few Hz and for elevated, persistent activity states of a few tens of Hz. Since the difference between these persistent activity states cannot be due to external factors coming from sensory inputs, this suggests that the underlying network dynamics might support coexisting balanced states at different firing rates. We use mean field techniques to study the possible existence of multiple balanced steady states in recurrent networks of current-based leaky integrate-and-fire (LIF) neurons. To assess the degree of balance of a steady state, we extend existing mean-field theories so that not only the firing rate, but also the coefficient of variation of the interspike interval distribution of the neurons, are determined self-consistently. Depending on the connectivity parameters of the network, we find bistable solutions of different types. If the local recurrent connectivity is mainly excitatory, the two stable steady states differ mainly in the mean current to the neurons. In this case, the mean drive in the elevated persistent activity state is suprathreshold and typically characterized by low spiking irregularity. If the local recurrent excitatory and inhibitory drives are both large and nearly balanced, or even dominated by inhibition, two stable states coexist, both with subthreshold current drive. In this case, the spiking variability in both the resting state and the mnemonic persistent state is large, but the balance condition implies parameter fine-tuning. Since the degree of required fine-tuning increases with network size and, on the other hand, the size of the fluctuations in the afferent current to the cells increases for small networks, overall we find that fluctuation-driven persistent activity in the very simplified type of models we analyze is not a robust phenomenon. Possible implications of considering more realistic models are discussed.
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Ekelmans, Pierre, Nataliya Kraynyukovas, and Tatjana Tchumatchenko. "Targeting operational regimes of interest in recurrent neural networks." PLOS Computational Biology 19, no. 5 (May 15, 2023): e1011097. http://dx.doi.org/10.1371/journal.pcbi.1011097.
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Neural computations emerge from local recurrent neural circuits or computational units such as cortical columns that comprise hundreds to a few thousand neurons. Continuous progress in connectomics, electrophysiology, and calcium imaging require tractable spiking network models that can consistently incorporate new information about the network structure and reproduce the recorded neural activity features. However, for spiking networks, it is challenging to predict which connectivity configurations and neural properties can generate fundamental operational states and specific experimentally reported nonlinear cortical computations. Theoretical descriptions for the computational state of cortical spiking circuits are diverse, including the balanced state where excitatory and inhibitory inputs balance almost perfectly or the inhibition stabilized state (ISN) where the excitatory part of the circuit is unstable. It remains an open question whether these states can co-exist with experimentally reported nonlinear computations and whether they can be recovered in biologically realistic implementations of spiking networks. Here, we show how to identify spiking network connectivity patterns underlying diverse nonlinear computations such as XOR, bistability, inhibitory stabilization, supersaturation, and persistent activity. We establish a mapping between the stabilized supralinear network (SSN) and spiking activity which allows us to pinpoint the location in parameter space where these activity regimes occur. Notably, we find that biologically-sized spiking networks can have irregular asynchronous activity that does not require strong excitation-inhibition balance or large feedforward input and we show that the dynamic firing rate trajectories in spiking networks can be precisely targeted without error-driven training algorithms.
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Sanchez-Vives, Maria V., Maurizio Mattia, Albert Compte, Maria Perez-Zabalza, Milena Winograd, Vanessa F. Descalzo, and Ramon Reig. "Inhibitory Modulation of Cortical Up States." Journal of Neurophysiology 104, no. 3 (September 2010): 1314–24. http://dx.doi.org/10.1152/jn.00178.2010.
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The balance between excitation and inhibition is critical in the physiology of the cerebral cortex. To understand the influence of inhibitory control on the emergent activity of the cortical network, inhibition was progressively blocked in a slice preparation that generates spontaneous rhythmic up states at a similar frequency to those occurring in vivo during slow-wave sleep or anesthesia. Progressive removal of inhibition induced a parametric shortening of up state duration and elongation of the down states, the frequency of oscillations decaying. Concurrently, a gradual increase in the network firing rate during up states occurred. The slope of transitions between up and down states was quantified for different levels of inhibition. The slope of upward transitions reflects the recruitment of the local network and was progressively increased when inhibition was decreased, whereas the speed of activity propagation became faster. Removal of inhibition eventually resulted in epileptiform activity. Whereas gradual reduction of inhibition induced linear changes in up/down states and their propagation, epileptiform activity was the result of a nonlinear transformation. A computational network model showed that strong recurrence plus activity-dependent hyperpolarizing currents were sufficient to account for the observed up state modulations and predicted an increase in activity-dependent hyperpolarization following up states when inhibition was decreased, which was confirmed experimentally.
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Sammon, M. "Geometry of respiratory phase switching." Journal of Applied Physiology 77, no. 5 (November 1, 1994): 2468–80. http://dx.doi.org/10.1152/jappl.1994.77.5.2468.
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A second-order ordinary differential equation is outlined for the temporal dynamics of the respiratory central pattern generator (RCPG). Recurrent interactions between central excitation and inhibition confine the breathing cycle to the interior of a heteroclinic orbit between switching points (saddle equilibria) located at end expiration (E-I) and end inspiration (I-E). Dynamics depend on four eigenvalues that control inspiratory drive (lambda), excitability of inspiratory off switch (omega 1; stage 1 expiration), rate of central excitation disinhibition (omega 2; stage 2 expiration), and damping of the oscillator (epsilon). Ratios omega 2/lambda and omega 1/lambda determine local E-I and I-E phase switching, whereas inspiratory-to-expiratory balance varies as omega 2/(lambda omega 1). Stable apnea is seen when (lambda omega 2)/epsilon is near zero; inspiratory apneusis is seen when (lambda omega 1)/epsilon is low. The equations provide formalisms for discussing phase switching, apneas, apneuses, phase resetting and singularities, rapid shallow breathing, postinhibitory rebound excitation, redundancy, gating within the RCPG, and behavioral control of breathing. The model is offered as an explicit alternative to the harmonic oscillator models that have been used in the past to describe RCPG function.
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Shao, Zhengwei, and Andreas Burkhalter. "Role of GABAB Receptor-Mediated Inhibition in Reciprocal Interareal Pathways of Rat Visual Cortex." Journal of Neurophysiology 81, no. 3 (March 1, 1999): 1014–24. http://dx.doi.org/10.1152/jn.1999.81.3.1014.
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Role of GABAB receptor-mediated inhibition in reciprocal interareal pathways of rat visual cortex. In neocortex, synaptic inhibition is mediated by γ-aminobutyric acid-A (GABAA) and GABAB receptors. By using intracellular and patch-clamp recordings in slices of rat visual cortex we studied the balance of excitation and inhibition in different intracortical pathways. The study was focused on the strength of fast GABAA- and slow GABAB-mediated inhibition in interareal forward and feedback connections between area 17 and the secondary, latero-medial visual area (LM). Our results demonstrate that in most layer 2/3 neurons forward inputs elicited excitatory postsynaptic potentials (EPSPs) that were followed by fast GABAA- and slow GABAB-mediated hyperpolarizing inhibitory postsynaptic potentials (IPSPs). These responses resembled those elicited by horizontal connections within area 17 and those evoked by stimulation of the layer 6/white matter border. In contrast, in the feedback pathway hyperpolarizing fast and slow IPSPs were rare. However weak fast and slow IPSPs were unmasked by bath application of GABAB receptor antagonists. Because in the feedback pathway disynaptic fast and slow IPSPs were rare, polysynaptic EPSPs were more frequent than in forward, horizontal, and interlaminar circuits and were activated over a broader stimulus range. In addition, in the feedback pathway large-amplitude polysynaptic EPSPs were longer lasting and showed a late component whose onset coincided with that of slow IPSPs. In the forward pathway these late EPSPs were only seen with stimulus intensities that were below the activation threshold of slow IPSPs. Unlike strong forward inputs, feedback stimuli of a wide range of intensities increased the rate of ongoing neuronal firing. Thus, when forward and feedback inputs are simultaneously active, feedback inputs may provide late polysynaptic excitation that can offset slow IPSPs evoked by forward inputs and in turn may promote recurrent excitation through local intracolumnar circuits. This may provide a mechanism by which feedback inputs from higher cortical areas can amplify afferent signals in lower areas.
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Pietra, Gianluca, Tiziana Bonifacino, Davide Talamonti, Giambattista Bonanno, Alessandro Sale, Lucia Galli, and Laura Baroncelli. "Visual Cortex Engagement in Retinitis Pigmentosa." International Journal of Molecular Sciences 22, no. 17 (August 30, 2021): 9412. http://dx.doi.org/10.3390/ijms22179412.
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Retinitis pigmentosa (RP) is a family of inherited disorders caused by the progressive degeneration of retinal photoreceptors. There is no cure for RP, but recent research advances have provided promising results from many clinical trials. All these therapeutic strategies are focused on preserving existing photoreceptors or substituting light-responsive elements. Vision recovery, however, strongly relies on the anatomical and functional integrity of the visual system beyond photoreceptors. Although the retinal structure and optic pathway are substantially preserved at least in early stages of RP, studies describing the visual cortex status are missing. Using a well-established mouse model of RP, we analyzed the response of visual cortical circuits to the progressive degeneration of photoreceptors. We demonstrated that the visual cortex goes through a transient and previously undescribed alteration in the local excitation/inhibition balance, with a net shift towards increased intracortical inhibition leading to improved filtering and decoding of corrupted visual inputs. These results suggest a compensatory action of the visual cortex that increases the range of residual visual sensitivity in RP.
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Yu, Dong, Tianyu Li, Qianming Ding, Yong Wu, Ziying Fu, Xuan Zhan, Lijian Yang, and Ya Jia. "Maintenance of delay-period activity in working memory task is modulated by local network structure." PLOS Computational Biology 20, no. 9 (September 3, 2024): e1012415. http://dx.doi.org/10.1371/journal.pcbi.1012415.
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Revealing the relationship between neural network structure and function is one central theme of neuroscience. In the context of working memory (WM), anatomical data suggested that the topological structure of microcircuits within WM gradient network may differ, and the impact of such structural heterogeneity on WM activity remains unknown. Here, we proposed a spiking neural network model that can replicate the fundamental characteristics of WM: delay-period neural activity involves association cortex but not sensory cortex. First, experimentally observed receptor expression gradient along the WM gradient network is reproduced by our network model. Second, by analyzing the correlation between different local structures and duration of WM activity, we demonstrated that small-worldness, excitation-inhibition balance, and cycle structures play crucial roles in sustaining WM-related activity. To elucidate the relationship between the structure and functionality of neural networks, structural circuit gradients in brain should also be subject to further measurement. Finally, combining anatomical data, we simulated the duration of WM activity across different brain regions, its maintenance relies on the interaction between local and distributed networks. Overall, network structural gradient and interaction between local and distributed networks are of great significance for WM.
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Liu, Sensen, and ShiNung Ching. "Recurrent Information Optimization with Local, Metaplastic Synaptic Dynamics." Neural Computation 29, no. 9 (September 2017): 2528–52. http://dx.doi.org/10.1162/neco_a_00993.
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We consider the problem of optimizing information-theoretic quantities in recurrent networks via synaptic learning. In contrast to feedforward networks, the recurrence presents a key challenge insofar as an optimal learning rule must aggregate the joint distribution of the whole network. This challenge, in particular, makes a local policy (i.e., one that depends on only pairwise interactions) difficult. Here, we report a local metaplastic learning rule that performs approximate optimization by estimating whole-network statistics through the use of several slow, nested dynamical variables. These dynamics provide the rule with both anti-Hebbian and Hebbian components, thus allowing for decorrelating and correlating learning regimes that can occur when either is favorable for optimality. We demonstrate the performance of the synthesized rule in comparison to classical BCM dynamics and use the networks to conduct history-dependent tasks that highlight the advantages of recurrence. Finally, we show the consistency of the resultant learned networks with notions of criticality, including balanced ratios of excitation and inhibition.
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Bharadwaj, Hari, and Varsha Mysore Athreya. "Effects of age-related cochlear deafferentation and central gain on auditory scene analysis." Journal of the Acoustical Society of America 154, no. 4_supplement (October 1, 2023): A333. http://dx.doi.org/10.1121/10.0023710.
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Animal models show that cochlear afferent nerve endings are more vulnerable than sensory hair cells to age-related damage. Because such cochlear deafferentation is not apparent in standard audiometry, the extent to which it contributes to deficits in human hearing is debated, and the intervening neural processes are poorly characterized. This presentation will describe our efforts to address these gaps through co-ordinated experiments in at-risk humans and a chinchilla model. Our results suggest that cochlear deafferentation is widespread in middle age despite clinically normal audiometric sensitivity. Furthermore, the resulting reduction in peripheral input appears to trigger compensatory central “gain” at the cortical level, likely through altered local balance of excitation and inhibition. Consistent with the important role of inhibition in parsing temporal regularities across different frequency components of sound, central gain is also associated with reduced ability to perceptually segregate acoustic scenes with multiple sources into individual perceptual streams. Taken together, our results suggest that age-related cochlear deafferentation may affect hearing not only by reducing the fidelity of input encoding but also by interfering with the central auditory system’s ability to extract targets in noisy environments.
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Shirhatti, Vinay, Poojya Ravishankar, and Supratim Ray. "Gamma oscillations in primate primary visual cortex are severely attenuated by small stimulus discontinuities." PLOS Biology 20, no. 6 (June 14, 2022): e3001666. http://dx.doi.org/10.1371/journal.pbio.3001666.
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Gamma oscillations (30 to 80 Hz) have been hypothesized to play an important role in feature binding, based on the observation that continuous long bars induce stronger gamma in the visual cortex than bars with a small gap. Recently, many studies have shown that natural images, which have discontinuities in several low-level features, do not induce strong gamma oscillations, questioning their role in feature binding. However, the effect of different discontinuities on gamma has not been well studied. To address this, we recorded spikes and local field potential from 2 monkeys while they were shown gratings with discontinuities in 4 attributes: space, orientation, phase, or contrast. We found that while these discontinuities only had a modest effect on spiking activity, gamma power drastically reduced in all cases, suggesting that gamma could be a resonant phenomenon. An excitatory–inhibitory population model with stimulus-tuned recurrent inputs showed such resonant properties. Therefore, gamma could be a signature of excitation–inhibition balance, which gets disrupted due to discontinuities.
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Pfeffer, Thomas, Adrian Ponce-Alvarez, Konstantinos Tsetsos, Thomas Meindertsma, Christoffer Julius Gahnström, Ruud Lucas van den Brink, Guido Nolte, Andreas Karl Engel, Gustavo Deco, and Tobias Hinrich Donner. "Circuit mechanisms for the chemical modulation of cortex-wide network interactions and behavioral variability." Science Advances 7, no. 29 (July 2021): eabf5620. http://dx.doi.org/10.1126/sciadv.abf5620.
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Influential theories postulate distinct roles of catecholamines and acetylcholine in cognition and behavior. However, previous physiological work reported similar effects of these neuromodulators on the response properties (specifically, the gain) of individual cortical neurons. Here, we show a double dissociation between the effects of catecholamines and acetylcholine at the level of large-scale interactions between cortical areas in humans. A pharmacological boost of catecholamine levels increased cortex-wide interactions during a visual task, but not rest. An acetylcholine boost decreased interactions during rest, but not task. Cortical circuit modeling explained this dissociation by differential changes in two circuit properties: the local excitation-inhibition balance (more strongly increased by catecholamines) and intracortical transmission (more strongly reduced by acetylcholine). The inferred catecholaminergic mechanism also predicted noisier decision-making, which we confirmed for both perceptual and value-based choice behavior. Our work highlights specific circuit mechanisms for shaping cortical network interactions and behavioral variability by key neuromodulatory systems.
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Farnan, Julia, Joshua Jackson, and Edward Hartsough. "FSMP-03. INVESTIGATING CO-OPTED ASTROCYTIC METABOLISM IN MELANOMA BRAIN METASTASIS." Neuro-Oncology Advances 3, Supplement_1 (March 1, 2021): i16—i17. http://dx.doi.org/10.1093/noajnl/vdab024.068.
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Abstract Melanoma, an aggressive form of skin cancer, frequently metastasizes to the brain. While peripheral melanoma is largely treatable, MBM fail to respond to current therapeutics and is a clear unmet clinical need. Initial clinical symptoms of Melanoma Brain Metastases (MBM) typically include headaches, seizures and other neurological deficits, suggesting that MBM disrupt normal brain functions. One of the major cell types that melanoma encounter and interact with during brain metastasis are astrocytes. Astrocytes, the most abundant cell in the brain, interact with neurons and the vasculature, provide trophic and energetic support to neurons, and regulate local blood flow. Metabolic pathways in astrocytes, particularly the glutamate-glutamine cycle, are essential for the recycling and resupply of neurotransmitters needed to maintain the excitation/inhibition balance. We propose that MBM co-opt astrocytic metabolism, fueling MBM growth, and deplete metabolic intermediates crucial for neuronal activity leading to altered neurologic function. We begin to unravel the metabolic interactions between astrocytes and MBM using novel modeling platforms with genetic and pharmacological tools to manipulate the tumor microenvironment. This project investigates the contribution of astrocytic metabolism to MBM growth. We intend on dissecting the distinct metabolic needs of metastatic brain melanoma in the CNS microenvironment and the subsequent neurological consequences. Completion of this project will provide a platform to study MBM and interaction with the local brain microenvironment. Inhibiting metabolic interactions between melanoma and glial cells may provide new avenue for therapeutic targeting of MBM.
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Riekki, Ruusu, Ivan Pavlov, Janne Tornberg, Sari E. Lauri, Matti S. Airaksinen, and Tomi Taira. "Altered Synaptic Dynamics and Hippocampal Excitability but Normal Long-Term Plasticity in Mice Lacking Hyperpolarizing GABAA Receptor-Mediated Inhibition in CA1 Pyramidal Neurons." Journal of Neurophysiology 99, no. 6 (June 2008): 3075–89. http://dx.doi.org/10.1152/jn.00606.2007.
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GABAA receptor (GABA-AR)-mediated inhibition is critical for proper operation of neuronal networks. Synaptic inhibition either shifts the membrane potential farther away from the action potential firing threshold (hyperpolarizing inhibition) or via increase in the membrane conductance shunts the excitatory currents. However, the relative importance of these different forms of inhibition on the hippocampal function is unclear. To study the functional consequences of the absence of hyperpolarizing inhibition, we have used KCC2-deficient mice (KCC2hy/null) maintaining only 15–20% of the neuron-specific K-Cl-cotransporter. Gramicidin-perforated patch-clamp recordings in hippocampal CA1 pyramidal cells revealed that the reversal potential of the GABA-AR-mediated postsynaptic currents ( EGABA-A) was ∼20 mV more positive in KCC2hy/null mice than in wild-type (WT) animals. The basic glutamatergic transmission appeared unaltered in the KCC2hy/null mice, yet they displayed lowered threshold for stimulation-induced synchronous afterdischarges in the CA1 area. Also fatigue of field excitatory postsynaptic potentials/excitatory postsynaptic currents in response to repetitious stimulation was smaller in KCC2hy/null mice, indicating altered synaptic dynamics. Interestingly, this effect was present also under blockade of GABA-ARs and was dependent on the extracellular K+ concentration. Moreover, there were no differences in the levels of either long-term potentiation or long-term depression between the genotypes. The local hippocampal CA1 network can in several aspects maintain its functional viability even in the absence of hyperpolarizing inhibition in pyramidal cells. Our results underscore the central role of shunting type of inhibition in controlling the neuronal excitation/inhibition balance. Moreover, our data demonstrate a novel, unexpected role for the KCC2, namely the modulation of properties of glutamatergic transmission during repetitious afferent activity.
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Potnis, V. V., Ketan G. Albhar, Pritamsinh Arjun Nanaware, and Vishal S. Pote. "A Review on Epilepsy and its Management." Journal of Drug Delivery and Therapeutics 10, no. 3 (May 15, 2020): 273–79. http://dx.doi.org/10.22270/jddt.v10i3.4090.
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Today, people face various types of stress in everyday fast life and most people in the world suffer from various neurological disorder. Epilepsy is one of the most common neurological disorders of the brain, affecting about 50 million people around the world, and 90% of them are coming from developing countries. Genetic factors and brain infection, stroke, tumors and epilepsy cause high fever. It imposes a great economic burden on the health systems of countries associated with stigma and discrimination against the patient and also his family in the community, in the workplace, school and home. Many patients with epilepsy suffer from severe emotional stress, behavioral disorders and extreme social isolation. There are many different types of seizure and mechanisms by which the brain generates seizures. The two features of generating seizures are hyperexcitability of neurons and a hyper synchronousneural circuits. A variety of mechanisms alters the balance between excitation and inhibition in predisposing brain local or generalized hyperexcitability region and a hypersynchronia. Purpose of the review is to discuss the history, epidemiology, etiology, pathophysiology, classification of epilepsy, symtomps, diagnosis, management of epilepsy and future trends.
Keywords: Anti-epileptic drugs, pathophysiology, seizures, epidemiology, hypersynchrony
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Kühn, Marco J., Lorenzo Talà, Yuki F. Inclan, Ramiro Patino, Xavier Pierrat, Iscia Vos, Zainebe Al-Mayyah, et al. "Mechanotaxis directs Pseudomonas aeruginosa twitching motility." Proceedings of the National Academy of Sciences 118, no. 30 (July 22, 2021): e2101759118. http://dx.doi.org/10.1073/pnas.2101759118.
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The opportunistic pathogen Pseudomonas aeruginosa explores surfaces using twitching motility powered by retractile extracellular filaments called type IV pili (T4P). Single cells twitch by sequential T4P extension, attachment, and retraction. How single cells coordinate T4P to efficiently navigate surfaces remains unclear. We demonstrate that P. aeruginosa actively directs twitching in the direction of mechanical input from T4P in a process called mechanotaxis. The Chp chemotaxis-like system controls the balance of forward and reverse twitching migration of single cells in response to the mechanical signal. Collisions between twitching cells stimulate reversals, but Chp mutants either always or never reverse. As a result, while wild-type cells colonize surfaces uniformly, collision-blind Chp mutants jam, demonstrating a function for mechanosensing in regulating group behavior. On surfaces, Chp senses T4P attachment at one pole, thereby sensing a spatially resolved signal. As a result, the Chp response regulators PilG and PilH control the polarization of the extension motor PilB. PilG stimulates polarization favoring forward migration, while PilH inhibits polarization, inducing reversal. Subcellular segregation of PilG and PilH efficiently orchestrates their antagonistic functions, ultimately enabling rapid reversals upon perturbations. The distinct localization of response regulators establishes a signaling landscape known as local excitation–global inhibition in higher-order organisms, identifying a conserved strategy to transduce spatially resolved signals.
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Gao, Xiao, and P. A. Robinson. "Importance of self-connections for brain connectivity and spectral connectomics." Biological Cybernetics 114, no. 6 (November 26, 2020): 643–51. http://dx.doi.org/10.1007/s00422-020-00847-5.
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AbstractSpectral analysis and neural field theory are used to investigate the role of local connections in brain connectivity matrices (CMs) that quantify connectivity between pairs of discretized brain regions. This work investigates how the common procedure of omitting such self-connections (i.e., the diagonal elements of CMs) in published studies of brain connectivity affects the properties of functional CMs (fCMs) and the mutually consistent effective CMs (eCMs) that correspond to them. It is shown that retention of self-connections in the fCM calculated from two-point activity covariances is essential for the fCM to be a true covariance matrix, to enable correct inference of the direct total eCMs from the fCM, and to ensure their compatibility with it; the deCM and teCM represent the strengths of direct connections and all connections between points, respectively. When self-connections are retained, inferred eCMs are found to have net inhibitory self-connections that represent the local inhibition needed to balance excitation via white matter fibers at longer ranges. This inference of spatially unresolved connectivity exemplifies the power of spectral connectivity methods, which also enable transformation of CMs to compact diagonal forms that allow accurate approximation of the fCM and total eCM in terms of just a few modes, rather than the full $$N^2$$ N 2 CM entries for connections between N brain regions. It is found that omission of fCM self-connections affects both local and long-range connections in eCMs, so they cannot be omitted even when studying the large-scale. Moreover, retention of local connections enables inference of subgrid short-range inhibitory connectivity. The results are verified and illustrated using the NKI-Rockland dataset from the University of Southern California Multimodal Connectivity Database. Deletion of self-connections is common in the field; this does not affect case-control studies but the present results imply that such fCMs must have self-connections restored before eCMs can be inferred from them.
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Yan, Jun, Yunfeng Zhang, and Günter Ehret. "Corticofugal Shaping of Frequency Tuning Curves in the Central Nucleus of the Inferior Colliculus of Mice." Journal of Neurophysiology 93, no. 1 (January 2005): 71–83. http://dx.doi.org/10.1152/jn.00348.2004.
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Plasticity of the auditory cortex can be induced by conditioning or focal cortical stimulation. The latter was used here to measure how stimulation in the tonotopy of the mouse primary auditory cortex influences frequency tuning in the midbrain central nucleus of the inferior colliculus (ICC). Shapes of collicular frequency tuning curves (FTCs) were quantified before and after cortical activation by measuring best frequencies, FTC bandwidths at various sound levels, level tolerance, Q-values, steepness of low- and high-frequency slopes, and asymmetries. We show here that all of these measures were significantly changed by focal cortical activation. The changes were dependent not only on the relationship of physiological properties between the stimulated cortical neurons and recorded collicular neurons but also on the tuning curve class of the collicular neuron. Cortical activation assimilated collicular FTC shapes; sharp and broad FTCs were changed to the shapes comparable to those of auditory nerve fibers. Plasticity in the ICC was organized in a center (excitatory)-surround (inhibitory) way with regard to the stimulated location (i.e., the frequency) of cortical tonotopy. This ensures, together with the spatial gradients of distribution of collicular FTC shapes, a sharp spectral filtering at the core of collicular frequency-band laminae and an increase in frequency selectivity at the periphery of the laminae. Mechanisms of FTC plasticity were suggested to comprise both corticofugal and local ICC components of excitatory and inhibitory modulation leading to a temporary change of the balance between excitation and inhibition in the ICC.
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Mostovenko, Ekaterina, Samantha Saunders, Pretal P. Muldoon, Lindsey Bishop, Matthew J. Campen, Aaron Erdely, and Andrew K. Ottens. "Carbon Nanotube Exposure Triggers a Cerebral Peptidomic Response: Barrier Compromise, Neuroinflammation, and a Hyperexcited State." Toxicological Sciences 182, no. 1 (April 21, 2021): 107–19. http://dx.doi.org/10.1093/toxsci/kfab042.
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Abstract The unique physicochemical properties of carbon nanomaterials and their ever-growing utilization generate a serious concern for occupational risk. Pulmonary exposure to these nanoparticles induces local and systemic inflammation, cardiovascular dysfunction, and even cognitive deficits. Although multiple routes of extrapulmonary toxicity have been proposed, the mechanism for and manner of neurologic effects remain minimally understood. Here, we examine the cerebral spinal fluid (CSF)-derived peptidomic fraction as a reflection of neuropathological alterations induced by pulmonary carbon nanomaterial exposure. Male C57BL/6 mice were exposed to 10 or 40 µg of multiwalled carbon nanotubes (MWCNT) by oropharyngeal aspiration. Serum and CSFs were collected 4 h post exposure. An enriched peptide fraction of both biofluids was analyzed using ion mobility-enabled data-independent mass spectrometry for label-free quantification. MWCNT exposure induced a prominent peptidomic response in the blood and CSF; however, correlation between fluids was limited. Instead, we determined that a MWCNT-induced peptidomic shift occurred specific to the CSF with 292 significant responses found that were not in serum. Identified MWCNT-responsive peptides depicted a mechanism involving aberrant fibrinolysis (fibrinopeptide A), blood-brain barrier permeation (homeobox protein A4), neuroinflammation (transmembrane protein 131L) with reactivity by astrocytes and microglia, and a pro-degradative (signal transducing adapter molecule, phosphoglycerate kinase), antiplastic (AF4/FMR2 family member 1, vacuolar protein sorting-associated protein 18) state with the excitation-inhibition balance shifted to a hyperexcited (microtubule-associated protein 1B) phenotype. Overall, the significant pathologic changes observed were consistent with early neurodegenerative disease and were diagnostically reflected in the CSF peptidome.
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Ichida, Jennifer M., Lars Schwabe, Paul C. Bressloff, and Alessandra Angelucci. "Response Facilitation From the “Suppressive” Receptive Field Surround of Macaque V1 Neurons." Journal of Neurophysiology 98, no. 4 (October 2007): 2168–81. http://dx.doi.org/10.1152/jn.00298.2007.
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In primary visual cortex (V1), neuronal responses to optimally oriented stimuli in the receptive field (RF) center are usually suppressed by iso-oriented stimuli in the RF surround. The mechanisms and pathways giving rise to surround modulation, a possible neural correlate of perceptual figure-ground segregation, are not yet identified. We previously proposed that highly divergent and fast-conducting top-down feedback connections are the substrate for fast modulation arising from the more distant regions of the surround. We have recently implemented this idea into a recurrent network model ( Schwabe et al. 2006 ). The purpose of this study was to test a crucial prediction of this feedback model, namely that the suppressive “far” surround of V1 neurons can be facilitatory under conditions that weakly activate neurons in the RF center. Using single-unit recordings in macaque V1, we found iso-orientation far-surround facilitation when the RF center was driven by a low-contrast stimulus and the far surround by a small annular stimulus. Suppression occurred when the center stimulus contrast or the size of the surround stimulus was increased. This suggests that center-surround interactions result from excitatory and inhibitory mechanisms of similar spatial extent, and that changes in the balance of local excitation and inhibition, induced by surround stimulation, determine whether facilitation or suppression occurs. In layer 4C, the main target of geniculocortical afferents, lacking long-range intra-cortical connections, far-surround facilitation was rare and large surround fields were absent. This strongly suggests that feedforward connections do not contribute to far-surround modulation and that the latter is generated by intra-cortical mechanisms, likely involving top-down feedback.
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Liang, Junhao, and Changsong Zhou. "Criticality enhances the multilevel reliability of stimulus responses in cortical neural networks." PLOS Computational Biology 18, no. 1 (January 31, 2022): e1009848. http://dx.doi.org/10.1371/journal.pcbi.1009848.
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Cortical neural networks exhibit high internal variability in spontaneous dynamic activities and they can robustly and reliably respond to external stimuli with multilevel features–from microscopic irregular spiking of neurons to macroscopic oscillatory local field potential. A comprehensive study integrating these multilevel features in spontaneous and stimulus–evoked dynamics with seemingly distinct mechanisms is still lacking. Here, we study the stimulus–response dynamics of biologically plausible excitation–inhibition (E–I) balanced networks. We confirm that networks around critical synchronous transition states can maintain strong internal variability but are sensitive to external stimuli. In this dynamical region, applying a stimulus to the network can reduce the trial-to-trial variability and shift the network oscillatory frequency while preserving the dynamical criticality. These multilevel features widely observed in different experiments cannot simultaneously occur in non-critical dynamical states. Furthermore, the dynamical mechanisms underlying these multilevel features are revealed using a semi-analytical mean-field theory that derives the macroscopic network field equations from the microscopic neuronal networks, enabling the analysis by nonlinear dynamics theory and linear noise approximation. The generic dynamical principle revealed here contributes to a more integrative understanding of neural systems and brain functions and incorporates multimodal and multilevel experimental observations. The E–I balanced neural network in combination with the effective mean-field theory can serve as a mechanistic modeling framework to study the multilevel neural dynamics underlying neural information and cognitive processes.
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Rudenko, A. "Features of the physical rehabilitation program of preschool children with the consequences of hip joint dysplasia." Scientific Journal of National Pedagogical Dragomanov University. Series 15. Scientific and pedagogical problems of physical culture (physical culture and sports), no. 4(124) (September 4, 2020): 79–85. http://dx.doi.org/10.31392/npu-nc.series15.2020.4(124).16.
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The physical rehabilitation program was developed based on the previous clinical and instrumental screening of functional disorders of the hip joints, formed as a result of dysplasia in preschool children. This program included preventive and rehabilitation blocks. The first block was used during the year and included: morning hygienic gymnastics, exercise minutes and pauses, awakening gymnastics, self-massage, hardening procedures (water procedures, walking barefoot, air and sun baths), psycho-emotional unloading. The second block included therapeutic gymnastics (fitballs, roles Zelart Grid elastic band Thera-band, balancing platform (hemisphere) BOSU, balance discs, traverse walls Traverse, step platforms), hydrokinesiotherapy, moving games, therapeutic massage (local, general, hydromassage), physiotherapy, orthopedic facilities. The developed program provides for the implementation of a comprehensive approach to restoring the physical and functional state of the preschool ORA through the use of game, simulation, traction, relaxation, stretching, special power, breathing, corrective and various coordination exercises. There are a lot of features and benefits of the proposed program, such as many different types of physical exercises for the development of motor skills and motor training, conducting physical exercises in an imitation way, strict dosing and exercise control, purposefully load weakened muscle groups, which depend on the correction of physiological curves of the spine and other segments of the torso and limbs, to diversify each exercise and give it a playful color, stimulate the cardiorespiratory system, using static and dynamic breathing exercises in combination with swinging movements, increase the elasticity and flexibility of the joints of the spine and limbs, through traction exercises and exercises with full range of motion, to form a stereotype of the correct posture, actively using the positive psycho-emotional state of the child, to harmonize the state of the nervous system (processes of excitation and inhibition) due to the alternation of emotional game exercises, strength exercises with overcoming resistance and relaxation exercises, to motivate children to actively and systematically perform special physical exercises.
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Spirin, Anatoly, Dmytro Borysiuk, Oleksandr Tsurkan, and Igor Tverdokhlib. "NFLUENCE OF VIBRATION ON THE ERGONOMIC INDICATORS OF THE PRODUCTION PROCESS." Vibrations in engineering and technology, no. 1 (108) (May 1, 2023): 45–56. http://dx.doi.org/10.37128/2306-8744-2023-1-5.
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Features of the impact of industrial vibration, the nature, depth and direction of physiological changes of various body systems depend on the level, frequency composition of vibrations and physiological properties of the human body. Vibration is one of the main causes of occupational diseases. The study of the sources of production vibration, the ways of its propagation, the specifics of the impact on the human body and protection against harmful effects is currently an urgent issue. The analysis of the latest sources shows that the majority of works consider individual elements of a complex system of ergonomic provision of safe working conditions in case of vibrational impact on workers. Therefore, there is a need to deepen the study of this issue, comprehensive consideration of the causes of vibration, its characteristics and specific effects on the worker's body, planning measures and means to minimize the consequences of its negative effects. There are two types of vibration: local, which primarily affects those organs of the human body that are in direct contact with vibrating elements, and general vibration, which causes the body to move in space and affects the entire body. The main parameters of vibration are amplitude and frequency of oscillations, speed and vibration acceleration. The effect of general vibration on the central nervous system leads to a disturbance in the balance between excitation and inhibition. Under the influence of vibration, workers become irritable, get tired quickly, feel drowsy (and sometimes, on the contrary, insomnia), work capacity decreases, the time it takes to complete production tasks increases, and the time of simple and complex reactions increases. The fight against the harmful effects of mechanical vibrations in most cases boils down to compliance with existing norms and rules. Also, a special role is played by means of protecting workers from the harmful effects of vibration. First of all, this is the improvement of the design of vehicles, machines, mechanisms and tools.
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Okun, Michael, and Ilan Lampl. "Balance of excitation and inhibition." Scholarpedia 4, no. 8 (2009): 7467. http://dx.doi.org/10.4249/scholarpedia.7467.
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Wu, Jian-Young, Li Guan, Li Bai, and Qian Yang. "Spatiotemporal Properties of an Evoked Population Activity in Rat Sensory Cortical Slices." Journal of Neurophysiology 86, no. 5 (November 1, 2001): 2461–74. http://dx.doi.org/10.1152/jn.2001.86.5.2461.
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We have examined the spatiotemporal properties of ensemble activity, an evoked all-or-none polysynaptic activity in rat neocortical slices. Ensemble activity occurred in cortical slices bathed in normal artificial cerebrospinal fluid (ACSF) and was evoked by a single electrical shock either to the white matter or directly to the cortical tissue. This activity was seen in slices of somatosensory and auditory cortices; in other cortical areas we have not been able to evoke it. The activity developed 10 to 250 ms poststimulus and lasted 280 ± 120 ms in local field potential (LFP) recordings. Voltage-sensitive dye imaging showed that this activity was an area of activation 0.8 ± 0.4 mm wide that propagated slowly (11.4 ± 6.2 mm/s, n = 60, 6 animals) in the horizontal direction. Due to this propagation, the actual duration in the whole tissue may be longer (∼400 ms) than that recorded by a single LFP electrode. Ensemble activity produced a low-amplitude optical signal (7–14% of the interictal-like spikes in the same tissue), suggesting a moderate net depolarization of the population. These were very different from hyperexcitable (epileptiform) events in the same tissue that had about 10 times the optical signal amplitude and propagated at 125 ± 24 mm/s ( n = 21, 6 animals). On a global spatial scale (∼0.8 mm wide in layers II–III) ensemble activity had a smooth waveform in voltage-sensitive dye signals (population transmembrane potential). On a local scale, field potential recordings showed large fluctuations with complex oscillations and substantial trial-to-trial variation. This suggests that oscillations in cortical circuits occurred only in small clusters of correlated neurons. Ensemble activity was sensitive to the excitation-inhibition balance of the local network. Antagonists of N-methyl-d-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and GABAa receptors, and muscarinic agonists and other modest manipulations such as increasing bath concentration of Mg2+ to 2.5–4 mM (normally at 2 mM), or K+ to 5–7 mM (normally 3 mM), all significantly reduced the probability of evoking the activity. The metabotropic glutamate receptor agonist, aminocyclopentane-1,3-dicarboxylic acid, blocked the activity at a low concentration (10–15 μM), while the antagonist (R,S)-α-methyl-4-carboxyphenylglycine had no effect even at high concentration (240 μM). Our data suggest that locally organized neuronal clusters may play a role in the organization of oscillatory activities in the gamma band and may participate in cortical integration/amplification occurring on a scale of ∼1 mm × 300 ms.
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Kirischuk, Sergei. "Keeping Excitation–Inhibition Ratio in Balance." International Journal of Molecular Sciences 23, no. 10 (May 20, 2022): 5746. http://dx.doi.org/10.3390/ijms23105746.
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Unrelated genetic mutations can lead to convergent manifestations of neurological disorders with similar behavioral phenotypes. Experimental data frequently show a lack of dramatic changes in neuroanatomy, indicating that the key cause of symptoms might arise from impairment in the communication between neurons. A transient imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) synaptic transmission (the E/I balance) during early development is generally considered to underlie the development of several neurological disorders in adults. However, the E/I ratio is a multidimensional variable. Synaptic contacts are highly dynamic and the actual strength of synaptic projections is determined from the balance between synaptogenesis and synaptic elimination. During development, relatively slow postsynaptic receptors are replaced by fast ones that allow for fast stimulus-locked excitation/inhibition. Using the binomial model of synaptic transmission allows for the reassessing of experimental data from different mouse models, showing that a transient E/I shift is frequently counterbalanced by additional pre- and/or postsynaptic changes. Such changes—for instance, the slowing down of postsynaptic currents by means of immature postsynaptic receptors—stabilize the average synaptic strength, but impair the timing of information flow. Compensatory processes and/or astrocytic signaling may represent possible targets for medical treatments of different disorders directed to rescue the proper information processing.
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Trevelyan, Andrew J., and Oliver Watkinson. "Does inhibition balance excitation in neocortex?" Progress in Biophysics and Molecular Biology 87, no. 1 (January 2005): 109–43. http://dx.doi.org/10.1016/j.pbiomolbio.2004.06.008.
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Liu, Yuhan, Vasily Grigorovsky, and Berj Bardakjian. "Excitation and Inhibition Balance Underlying Epileptiform Activity." IEEE Transactions on Biomedical Engineering 67, no. 9 (September 2020): 2473–81. http://dx.doi.org/10.1109/tbme.2019.2963430.
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Safdie, Gracia, Jana F. Liewald, Sarah Kagan, Emil Battat, Alexander Gottschalk, and Millet Treinin. "RIC-3 phosphorylation enables dual regulation of excitation and inhibition of Caenorhabditis elegans muscle." Molecular Biology of the Cell 27, no. 19 (October 2016): 2994–3003. http://dx.doi.org/10.1091/mbc.e16-05-0265.
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Brain function depends on a delicate balance between excitation and inhibition. Similarly, Caenorhabditis elegans motor system function depends on a precise balance between excitation and inhibition, as C. elegans muscles receive both inhibitory, GABAergic and excitatory, cholinergic inputs from motor neurons. Here we show that phosphorylation of the ER-resident chaperone of nicotinic acetylcholine receptors, RIC-3, leads to increased muscle excitability. RIC-3 phosphorylation at Ser-164 depends on opposing functions of the phosphatase calcineurin (TAX-6), and of the casein kinase II homologue KIN-10. Effects of calcineurin down-regulation and of phosphorylated RIC-3 on muscle excitability are mediated by GABAA receptor inhibition. Thus RIC-3 phosphorylation enables effects of this chaperone on GABAA receptors in addition to nAChRs. This dual effect provides coordinated regulation of excitation and inhibition and enables fine-tuning of the excitation–inhibition balance. Moreover, regulation of inhibitory GABAA signaling by calcineurin, a calcium- and calmodulin-dependent phosphatase, enables homeostatic balancing of excitation and inhibition.
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Lopatina, Olga L., Yulia K. Komleva, Yana V. Gorina, Raisa Ya Olovyannikova, Lyudmila V. Trufanova, Takanori Hashimoto, Tetsuya Takahashi, et al. "Oxytocin and excitation/inhibition balance in social recognition." Neuropeptides 72 (December 2018): 1–11. http://dx.doi.org/10.1016/j.npep.2018.09.003.
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Gao, Richard, Erik J. Peterson, and Bradley Voytek. "Inferring synaptic excitation/inhibition balance from field potentials." NeuroImage 158 (September 2017): 70–78. http://dx.doi.org/10.1016/j.neuroimage.2017.06.078.
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Lee, Yong-Seok. "Tipping excitation/inhibition balance in autism mouse models." IBRO Reports 6 (September 2019): S6—S7. http://dx.doi.org/10.1016/j.ibror.2019.07.004.
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Tao, Huizhong W., Ya-tang Li, and Li I. Zhang. "Formation of excitation-inhibition balance: inhibition listens and changes its tune." Trends in Neurosciences 37, no. 10 (October 2014): 528–30. http://dx.doi.org/10.1016/j.tins.2014.09.001.
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Smith, Anika K., Alex R. Wade, Kirsty EH Penkman, and Daniel H. Baker. "Dietary modulation of cortical excitation and inhibition." Journal of Psychopharmacology 31, no. 5 (April 4, 2017): 632–37. http://dx.doi.org/10.1177/0269881117699613.
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The balance of excitatory and inhibitory neurotransmitters in the brain affects both neural responses and behaviour in humans and animals. Here we investigated whether dietary intervention aimed at increasing levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) can influence neural responses to basic sensory stimuli. Using a steady-state electroencephalography (EEG) paradigm, we found that the neural response to visual patterns was reduced in individuals who consumed a yeast extract product rich in substances associated with the production of GABA (glutamate and B vitamins), but not in a control group who consumed a placebo substance ( n = 14 per group). This demonstrates that the balance of excitation and inhibition in the brain can be influenced by dietary interventions, suggesting possible clinical benefits in conditions (e.g. epilepsy) where inhibition is abnormal.
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Durieux, Alice M. S., Jamie Horder, and Marija M. Petrinovic. "Neuroligin-2 and the tightrope of excitation/inhibition balance in the prefrontal cortex." Journal of Neurophysiology 115, no. 1 (January 1, 2016): 5–7. http://dx.doi.org/10.1152/jn.00703.2015.
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Excitation/inhibition imbalance is implicated in symptoms of neuropsychiatric disorders. We discuss a study by Liang et al. ( Mol Psychiatry 20: 850–859, 2015) demonstrating that the conditional knockout of neuroligin-2, a postsynaptic adhesion protein, in the prefrontal cortex of adult mice results in alterations in inhibitory synaptic properties. However, behavioral impairments emerged prior to the development of detectable changes in excitation/inhibition ratio. This suggests there may be network-specific excitation/inhibition ratios, some of which are more vulnerable to disruption than others.
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Aleksandrova, Lily R., Wenlin Chen, and Yu Tian Wang. "An Erbin Story: Amygdala Excitation-Inhibition Balance in Anxiety." Biological Psychiatry 87, no. 10 (May 2020): 872–74. http://dx.doi.org/10.1016/j.biopsych.2020.03.005.
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He, Hai-yan, and Hollis T. Cline. "What Is Excitation/Inhibition and How Is It Regulated? A Case of the Elephant and the Wisemen." Journal of Experimental Neuroscience 13 (January 2019): 117906951985937. http://dx.doi.org/10.1177/1179069519859371.
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The balance between excitation and inhibition in neuronal circuits has drawn more and more attention in recent years, due to its proposed multifaceted functions in the normal neural circuit as well as its potential roles in the etiology of many neurological disorders. Here, we discuss the importance of clearly defining excitation/inhibition by experimental measurements and the implications of some recent studies to our understanding of the regulation of excitation/inhibition at the neuronal level.
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Abbasi, Samira, Annemarie Wolff, Yasir Çatal, and Georg Northoff. "Increased noise relates to abnormal excitation-inhibition balance in schizophrenia: a combined empirical and computational study." Cerebral Cortex, August 10, 2023. http://dx.doi.org/10.1093/cercor/bhad297.
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Abstract Electroencephalography studies link sensory processing issues in schizophrenia to increased noise level—noise here is background spontaneous activity—as measured by the signal-to-noise ratio. The mechanism, however, of such increased noise is unknown. We investigate if this relates to changes in cortical excitation-inhibition balance, which has been observed to be atypical in schizophrenia, by combining electroencephalography and computational modeling. Our electroencephalography task results, for which the local field potentials can be used as a proxy, show lower signal-to-noise ratio due to higher noise in schizophrenia. Both electroencephalography rest and task states exhibit higher levels of excitation in the functional excitation-inhibition (as a proxy of excitation-inhibition balance). This suggests a relationship between increased noise and atypical excitation in schizophrenia, which was addressed by using computational modeling. A Leaky Integrate-and-Fire model was used to simulate the effects of varying degrees of noise on excitation-inhibition balance, local field potential, NMDA current, and . Results show a noise-related increase in the local field potential, excitation in excitation-inhibition balance, pyramidal NMDA current, and spike rate. Mutual information and mediation analysis were used to explore a cross-level relationship, showing that the cortical local field potential plays a key role in transferring the effect of noise to the cellular population level of NMDA.
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Liang, Junhao, Zhuda Yang, and Changsong Zhou. "Excitation–Inhibition Balance, Neural Criticality, and Activities in Neuronal Circuits." Neuroscientist, January 31, 2024. http://dx.doi.org/10.1177/10738584231221766.
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Neural activities in local circuits exhibit complex and multilevel dynamic features. Individual neurons spike irregularly, which is believed to originate from receiving balanced amounts of excitatory and inhibitory inputs, known as the excitation–inhibition balance. The spatial-temporal cascades of clustered neuronal spikes occur in variable sizes and durations, manifested as neural avalanches with scale-free features. These may be explained by the neural criticality hypothesis, which posits that neural systems operate around the transition between distinct dynamic states. Here, we summarize the experimental evidence for and the underlying theory of excitation–inhibition balance and neural criticality. Furthermore, we review recent studies of excitatory–inhibitory networks with synaptic kinetics as a simple solution to reconcile these two apparently distinct theories in a single circuit model. This provides a more unified understanding of multilevel neural activities in local circuits, from spontaneous to stimulus-response dynamics.