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Feedforward Inhibition

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https://www.readbyqxmd.com/read/28808338/a-dynamical-framework-for-complex-fractional-killing
#1
Richard Ballweg, Andrew L Paek, Tongli Zhang
When chemotherapy drugs are applied to tumor cells with the same or similar genotypes, some cells are killed, while others survive. This fractional killing contributes to drug resistance in cancer. Through an incoherent feedforward loop, chemotherapy drugs not only activate p53 to induce cell death, but also promote the expression of apoptosis inhibitors which inhibit cell death. Consequently, cells in which p53 is activated early undergo apoptosis while cells in which p53 is activated late survive. The incoherent feedforward loop and the essential role of p53 activation timing makes fractional killing a complex dynamical challenge, which is hard to understand with intuition alone...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747874/the-functioning-of-a-cortex-without-layers
#2
REVIEW
Julien Guy, Jochen F Staiger
A major hallmark of cortical organization is the existence of a variable number of layers, i.e., sheets of neurons stacked on top of each other, in which neurons have certain commonalities. However, even for the neocortex, variable numbers of layers have been described and it is just a convention to distinguish six layers from each other. Whether cortical layers are a structural epiphenomenon caused by developmental dynamics or represent a functionally important modularization of cortical computation is still unknown...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28736520/combined-effects-of-feedforward-inhibition-and-excitation-in-thalamocortical-circuit-on-the-transitions-of-epileptic-seizures
#3
Denggui Fan, Lixia Duan, Qian Wang, Guoming Luan
The mechanisms underlying electrophysiologically observed two-way transitions between absence and tonic-clonic epileptic seizures in cerebral cortex remain unknown. The interplay within thalamocortical network is believed to give rise to these epileptic multiple modes of activity and transitions between them. In particular, it is thought that in some areas of cortex there exists feedforward inhibition from specific relay nucleus of thalamus (TC) to inhibitory neuronal population (IN) which has even more stronger functions on cortical activities than the known feedforward excitation from TC to excitatory neuronal population (EX)...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/28698210/apobec3a-and-apobec3b-activities-render-cancer-cells-susceptible-to-atr-inhibition
#4
Rémi Buisson, Michael S Lawrence, Cyril H Benes, Lee Zou
The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like APOBEC3A and APOBEC3B have emerged as key mutation drivers in cancer. Here, we show that APOBEC3A and APOBEC3B activities impose a unique type of replication stress by inducing abasic sites at replication forks. In contrast to cells under other types of replication stress, APOBEC3A-expressing cells were selectively sensitive to ATR inhibitors (ATRi), but not to a variety of DNA replication inhibitors and DNA-damaging drugs. In proliferating cells, APOBEC3A modestly elicited ATR but not ATM...
July 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/28696588/feedforward-inhibition-is-randomly-wired-from-individual-granule-cells-onto-ca3-pyramidal-cells
#5
Máté Neubrandt, Viktor János Oláh, János Brunner, János Szabadics
Feedforward inhibition (FFI) between the dentate gyrus (DG) and CA3 sparsifies and shapes memory- and spatial navigation-related activities. However, our understanding of this prototypical FFI circuit lacks essential details, as the wiring of FFI is not yet mapped between individual DG granule cells (GCs) and CA3 pyramidal cells (PCs). Importantly, theoretically opposite network contributions are possible depending on whether the directly excited PCs are differently inhibited than the non-excited PCs. Therefore, to better understand FFI wiring schemes, we compared the prevalence of disynaptic inhibitory postsynaptic events (diIPSCs) between pairs of individually recorded GC axons or somas and PCs, some of which were connected by monosynaptic excitation, while others were not...
July 11, 2017: Hippocampus
https://www.readbyqxmd.com/read/28625487/distinct-feedforward-and-feedback-effects-of-microstimulation-in-visual-cortex-reveal-neural-mechanisms-of-texture-segregation
#6
P Christiaan Klink, Bruno Dagnino, Marie-Alice Gariel-Mathis, Pieter R Roelfsema
The visual cortex is hierarchically organized, with low-level areas coding for simple features and higher areas for complex ones. Feedforward and feedback connections propagate information between areas in opposite directions, but their functional roles are only partially understood. We used electrical microstimulation to perturb the propagation of neuronal activity between areas V1 and V4 in monkeys performing a texture-segregation task. In both areas, microstimulation locally caused a brief phase of excitation, followed by inhibition...
July 5, 2017: Neuron
https://www.readbyqxmd.com/read/28617659/inhibitory-interneurons-in-the-retina-types-circuitry-and-function
#7
Jeffrey S Diamond
Visual signals in the vertebrate retina are shaped by feedback and feedforward inhibition in two synaptic layers. In one, horizontal cells establish fundamental center-surround receptive-field properties via morphologically and physiologically complex synapses with photoreceptors and bipolar cells. In the other, a panoply of amacrine cells imbue ganglion cell responses with spatiotemporally complex information about the visual world. Here, I review current ideas about horizontal cell signaling, considering the evidence for and against the leading, competing theories...
June 15, 2017: Annual Review of Vision Science
https://www.readbyqxmd.com/read/28599115/recurrent-information-optimization-with-local-metaplastic-synaptic-dynamics
#8
Sensen Liu, ShiNung Ching
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...
June 9, 2017: Neural Computation
https://www.readbyqxmd.com/read/28598717/inhibitory-plasticity-balance-control-and-codependence
#9
Guillaume Hennequin, Everton J Agnes, Tim P Vogels
Inhibitory neurons, although relatively few in number, exert powerful control over brain circuits. They stabilize network activity in the face of strong feedback excitation and actively engage in computations. Recent studies reveal the importance of a precise balance of excitation and inhibition in neural circuits, which often requires exquisite fine-tuning of inhibitory connections. We review inhibitory synaptic plasticity and its roles in shaping both feedforward and feedback control. We discuss the necessity of complex, codependent plasticity mechanisms to build nontrivial, functioning networks, and we end by summarizing experimental evidence of such interactions...
July 25, 2017: Annual Review of Neuroscience
https://www.readbyqxmd.com/read/28591219/mechanisms-underlying-a-thalamocortical-transformation-during-active-tactile-sensation
#10
Diego Adrian Gutnisky, Jianing Yu, Samuel Andrew Hires, Minh-Son To, Michael Ross Bale, Karel Svoboda, David Golomb
During active somatosensation, neural signals expected from movement of the sensors are suppressed in the cortex, whereas information related to touch is enhanced. This tactile suppression underlies low-noise encoding of relevant tactile features and the brain's ability to make fine tactile discriminations. Layer (L) 4 excitatory neurons in the barrel cortex, the major target of the somatosensory thalamus (VPM), respond to touch, but have low spike rates and low sensitivity to the movement of whiskers. Most neurons in VPM respond to touch and also show an increase in spike rate with whisker movement...
June 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28498919/chemicogenetic-restoration-of-the-prefrontal-cortex-to-amygdala-pathway-ameliorates-stress-induced-deficits
#11
Jing Wei, Ping Zhong, Luye Qin, Tao Tan, Zhen Yan
Corticosteroid stress hormones exert a profound impact on cognitive and emotional processes. Understanding the neuronal circuits that are altered by chronic stress is important for counteracting the detrimental effects of stress in a brain region- and cell type-specific manner. Using the chemogenetic tool, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), which enables the remote, noninvasive and long-lasting modulation of cellular activity and signal transduction in discrete neuronal populations in vivo, we sought to identify the specific pathways that play an essential role in stress responses...
May 11, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28472661/chronic-loss-of-ca2-transmission-leads-to-hippocampal-hyperexcitability
#12
Roman Boehringer, Denis Polygalov, Arthur J Y Huang, Steven J Middleton, Vincent Robert, Marie E Wintzer, Rebecca A Piskorowski, Vivien Chevaleyre, Thomas J McHugh
Hippocampal CA2 pyramidal cells project into both the neighboring CA1 and CA3 subfields, leaving them well positioned to influence network physiology and information processing for memory and space. While recent work has suggested unique roles for CA2, including encoding position during immobility and generating ripple oscillations, an interventional examination of the integrative functions of these connections has yet to be reported. Here we demonstrate that CA2 recruits feedforward inhibition in CA3 and that chronic genetically engineered shutdown of CA2-pyramidal-cell synaptic transmission consequently results in increased excitability of the recurrent CA3 network...
May 3, 2017: Neuron
https://www.readbyqxmd.com/read/28471714/circuits-and-mechanisms-for-surround-modulation-in-visual-cortex
#13
Alessandra Angelucci, Maryam Bijanzadeh, Lauri Nurminen, Frederick Federer, Sam Merlin, Paul C Bressloff
Surround modulation (SM) is a fundamental property of sensory neurons in many species and sensory modalities. SM is the ability of stimuli in the surround of a neuron's receptive field (RF) to modulate (typically suppress) the neuron's response to stimuli simultaneously presented inside the RF, a property thought to underlie optimal coding of sensory information and important perceptual functions. Understanding the circuit and mechanisms for SM can reveal fundamental principles of computations in sensory cortices, from mouse to human...
July 25, 2017: Annual Review of Neuroscience
https://www.readbyqxmd.com/read/28461661/measuring-feedforward-inhibition-and-its-impact-on-local-circuit-function
#14
Court Hull
This protocol describes a series of approaches to measure feedforward inhibition in acute brain slices from the cerebellar cortex. Using whole-cell voltage and current clamp recordings from Purkinje cells in conjunction with electrical stimulation of the parallel fibers, these methods demonstrate how to measure the relationship between excitation and inhibition in a feedforward circuit. This protocol also describes how to measure the impact of feedforward inhibition on Purkinje cell excitability, with an emphasis on spike timing...
May 1, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28438969/intracellular-in-vivo-dynamics-of-thalamocortical-synapses-in-visual-cortex
#15
Madineh Sedigh-Sarvestani, Leif Vigeland, Ivan Fernandez-Lamo, M Morgan Taylor, Larry A Palmer, Diego Contreras
Seminal studies of the thalamocortical circuit in the visual system of the cat have been central to our understanding of sensory encoding. However, thalamocortical synaptic properties remain poorly understood. We used paired recordings, in the lateral geniculate nucleus (LGN) and primary visual cortex (V1), to provide the first in vivo characterization of sensory-driven thalamocortical potentials in V1. The amplitudes of EPSPs we characterized were smaller than those previously reported in vitro Consistent with prior findings, connected LGN-V1 pairs were only found when their receptive fields (RFs) overlapped, and the probability of connection increased steeply with degree of RF overlap and response similarity...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432122/dual-regulation-of-stat1-and-stat3-by-the-tumor-suppressor-protein-pml-contributes-to-interferon-%C3%AE-mediated-inhibition-of-angiogenesis
#16
COMPARATIVE STUDY
Kuo-Sheng Hsu, Xuan Zhao, Xiwen Cheng, Dongyin Guan, Ganapati H Mahabeleshwar, Yu Liu, Ernest Borden, Mukesh K Jain, Hung-Ying Kao
IFNs are effective in inhibiting angiogenesis in preclinical models and in treating several angioproliferative disorders. However, the detailed mechanisms of IFNα-mediated anti-angiogenesis are not completely understood. Stat1/2/3 and PML are IFNα downstream effectors and are pivotal regulators of angiogenesis. Here, we investigated PML's role in the regulation of Stat1/2/3 activity. In Pml knock-out (KO) mice, ablation of Pml largely reduces IFNα angiostatic ability in Matrigel plug assays. This suggested an essential role for PML in IFNα's anti-angiogenic function...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28374012/activation-of-ras-erk-signaling-and-gsk-3-by-amyloid-precursor-protein-and-amyloid-beta-facilitates-neurodegeneration-in-alzheimer-s-disease
#17
Lisa Kirouac, Alexander J Rajic, David H Cribbs, Jaya Padmanabhan
It is widely accepted that amyloid β (Aβ) generated from amyloid precursor protein (APP) oligomerizes and fibrillizes to form neuritic plaques in Alzheimer's disease (AD), yet little is known about the contribution of APP to intracellular signaling events preceding AD pathogenesis. The data presented here demonstrate that APP expression and neuronal exposure to oligomeric Aβ42 enhance Ras/ERK signaling cascade and glycogen synthase kinase 3 (GSK-3) activation. We find that RNA interference (RNAi)-directed knockdown of APP in B103 rat neuroblastoma cells expressing APP inhibits Ras-ERK signaling and GSK-3 activation, indicating that APP acts upstream of these signal transduction events...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28334225/pom-thalamocortical-input-drives-layer-specific-microcircuits-in-somatosensory-cortex
#18
Nicholas J Audette, Joanna Urban-Ciecko, Megumi Matsushita, Alison L Barth
Higher-order thalamic nuclei, such as the posterior medial nucleus (POm) in the somatosensory system or the pulvinar in the visual system, densely innervate the cortex and can influence perception and plasticity. To systematically evaluate how higher-order thalamic nuclei can drive cortical circuits, we investigated cell-type selective responses to POm stimulation in mouse primary somatosensory (barrel) cortex, using genetically targeted whole-cell recordings in acute brain slices. We find that ChR2-evoked thalamic input selectively targets specific cell types in the neocortex, revealing layer-specific modules for the summation and processing of POm input...
March 10, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28329692/organization-of-functional-long-range-circuits-controlling-the-activity-of-serotonergic-neurons-in-the-dorsal-raphe-nucleus
#19
Li Zhou, Ming-Zhe Liu, Qing Li, Juan Deng, Di Mu, Yan-Gang Sun
Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN) of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28283576/glucocorticoid-and-cytokine-crosstalk-feedback-feedforward-and-co-regulatory-interactions-determine-repression-or-resistance
#20
REVIEW
Robert Newton, Suharsh Shah, Mohammed O Altonsy, Antony N Gerber
Inflammatory signals induce feedback and feedforward systems that provide temporal control. Although glucocorticoids can repress inflammatory gene expression, glucocorticoid receptor recruitment increases expression of negative feedback and feedforward regulators, including the phosphatase, DUSP1, the ubiquitin-modifying enzyme, TNFAIP3, or the mRNA-destabilizing protein, ZFP36. Moreover, glucocorticoid receptor cooperativity with factors, including nuclear factor-κB (NF-κB), may enhance regulator expression to promote repression...
April 28, 2017: Journal of Biological Chemistry
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