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Feedforward Inhibition

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https://www.readbyqxmd.com/read/28069808/kinetic-modeling-and-analysis-of-the-akt-mechanistic-target-of-rapamycin-complex-1-mtorc1-signaling-axis-reveals-cooperative-feedforward-regulation
#1
Anisur Rahman, Jason M Haugh
Mechanistic target of rapamycin complex 1 (mTORC1) controls biosynthesis and has been implicated in uncontrolled cell growth in cancer. Although many details of mTORC1 regulation are well understood, a systems-level, predictive framework synthesizing those details is currently lacking. We constructed various mathematical models of mTORC1 activation mediated by Akt and aligned the model outputs to kinetic data acquired for growth factor-stimulated cells. A model based on a putative feedforward loop orchestrated by Akt consistently predicted how the pathway was altered by depletion of key regulatory proteins...
January 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28053043/habenula-induced-inhibition-of-midbrain-dopamine-neurons-is-diminished-by-lesions-of-the-rostromedial-tegmental-nucleus
#2
P Leon Brown, Heather Palacorolla, Dana Brady, Katelyn Riegger, Greg I Elmer, Paul D Shepard
: Neurons in the lateral habenula (LHb) are transiently activated by aversive events and have been implicated in associative learning. Functional changes associated with tonic and phasic activation of the LHb are often attributed to a corresponding inhibition of midbrain dopamine (DA) neurons. Activation of GABAergic neurons in the rostromedial tegmental nucleus (RMTg), a region that receives dense projections from the LHb and projects strongly to midbrain monoaminergic nuclei, is believed to underlie the transient inhibition of DA neurons attributed to activation of the LHb...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28041912/a-constitutive-intrinsic-inflammatory-signaling-circuit-composed-of-mir-196b-meis2-ppp3cc-and-p65-drives-prostate-cancer-castration-resistance
#3
Ji-Hak Jeong, Sun-Jin Park, Shohreh Iravani Dickinson, Jun-Li Luo
Androgen deprivation therapy is the most effective treatment for advanced prostate cancer, but almost all cancer eventually becomes castration resistant, and the underlying mechanisms are largely unknown. Here, we show that an intrinsic constitutively activated feedforward signaling circuit composed of IκBα/NF-κB(p65), miR-196b-3p, Meis2, and PPP3CC is formed during the emergence of castration-resistant prostate cancer (CRPC). This circuit controls the expression of stem cell transcription factors that drives the high tumorigenicity of CRPC cells...
January 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28030651/retinal-lateral-inhibition-provides-the-biological-basis-of-long-range-spatial-induction
#4
Jihyun Yeonan-Kim, Marcelo Bertalmío
Retinal lateral inhibition is one of the conventional efficient coding mechanisms in the visual system that is produced by interneurons that pool signals over a neighborhood of presynaptic feedforward cells and send inhibitory signals back to them. Thus, the receptive-field (RF) of a retinal ganglion cell has a center-surround receptive-field (RF) profile that is classically represented as a difference-of-Gaussian (DOG) adequate for efficient spatial contrast coding. The DOG RF profile has been attributed to produce the psychophysical phenomena of brightness induction, in which the perceived brightness of an object is affected by that of its vicinity, either shifting away from it (brightness contrast) or becoming more similar to it (brightness assimilation) depending on the size of the surfaces surrounding the object...
2016: PloS One
https://www.readbyqxmd.com/read/28003347/olfactory-bulb-deep-short-axon-cells-mediate-widespread-inhibition-of-tufted-cell-apical-dendrites
#5
Shawn D Burton, Greg LaRocca, Annie Liu, Claire E J Cheetham, Nathaniel N Urban
: In the main olfactory bulb (MOB), the first station of sensory processing in the olfactory system, GABAergic interneuron signaling shapes principal neuron activity to regulate olfaction. Lack of known selective markers for MOB interneurons has strongly impeded cell type-selective investigation of interneuron function, however. Here, we identify the first selective marker of glomerular layer-projecting deep short-axon cells (GL-dSACs) and systematically investigate the structure, abundance, intrinsic physiology, feedforward sensory input, neuromodulation, synaptic output, and functional role of GL-dSACs in the mouse MOB circuit...
December 21, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27989802/nerve-growth-factor-promotes-gastric-tumorigenesis-through-aberrant-cholinergic-signaling
#6
Yoku Hayakawa, Kosuke Sakitani, Mitsuru Konishi, Samuel Asfaha, Ryota Niikura, Hiroyuki Tomita, Bernhard W Renz, Yagnesh Tailor, Marina Macchini, Moritz Middelhoff, Zhengyu Jiang, Takayuki Tanaka, Zinaida A Dubeykovskaya, Woosook Kim, Xiaowei Chen, Aleksandra M Urbanska, Karan Nagar, Christoph B Westphalen, Michael Quante, Chyuan-Sheng Lin, Michael D Gershon, Akira Hara, Chun-Mei Zhao, Duan Chen, Daniel L Worthley, Kazuhiko Koike, Timothy C Wang
Within the gastrointestinal stem cell niche, nerves help to regulate both normal and neoplastic stem cell dynamics. Here, we reveal the mechanisms underlying the cancer-nerve partnership. We find that Dclk1(+) tuft cells and nerves are the main sources of acetylcholine (ACh) within the gastric mucosa. Cholinergic stimulation of the gastric epithelium induced nerve growth factor (NGF) expression, and in turn NGF overexpression within gastric epithelium expanded enteric nerves and promoted carcinogenesis. Ablation of Dclk1(+) cells or blockade of NGF/Trk signaling inhibited epithelial proliferation and tumorigenesis in an ACh muscarinic receptor-3 (M3R)-dependent manner, in part through suppression of yes-associated protein (YAP) function...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/27989801/molecular-checkpoint-decisions-made-by-subverted-vascular-niche-transform-indolent-tumor-cells-into-chemoresistant-cancer-stem-cells
#7
Zhongwei Cao, Joseph M Scandura, Giorgio G Inghirami, Koji Shido, Bi-Sen Ding, Shahin Rafii
Tumor-associated endothelial cells (TECs) regulate tumor cell aggressiveness. However, the core mechanism by which TECs confer stem cell-like activity to indolent tumors is unknown. Here, we used in vivo murine and human tumor models to identify the tumor-suppressive checkpoint role of TEC-expressed insulin growth factor (IGF) binding protein-7 (IGFBP7/angiomodulin). During tumorigenesis, IGFBP7 blocks IGF1 and inhibits expansion and aggresiveness of tumor stem-like cells (TSCs) expressing IGF1 receptor (IGF1R)...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/27976716/dendritic-excitation-inhibition-balance-shapes-cerebellar-output-during-motor-behaviour
#8
Marta Jelitai, Paolo Puggioni, Taro Ishikawa, Arianna Rinaldi, Ian Duguid
Feedforward excitatory and inhibitory circuits regulate cerebellar output, but how these circuits interact to shape the somatodendritic excitability of Purkinje cells during motor behaviour remains unresolved. Here we perform dendritic and somatic patch-clamp recordings in vivo combined with optogenetic silencing of interneurons to investigate how dendritic excitation and inhibition generates bidirectional (that is, increased or decreased) Purkinje cell output during self-paced locomotion. We find that granule cells generate a sustained depolarization of Purkinje cell dendrites during movement, which is counterbalanced by variable levels of feedforward inhibition from local interneurons...
December 15, 2016: Nature Communications
https://www.readbyqxmd.com/read/27929113/a-feedforward-inhibitory-circuit-mediated-by-cb1-expressing-fast-spiking-interneurons-in-the-nucleus-accumbens
#9
William J Wright, Oliver M Schlüter, Yan Dong
The nucleus accumbens (NAc) gates motivated behaviors through the functional output of principle medium spiny neurons (MSNs), whereas dysfunctional output of NAc MSNs contributes to a variety of psychiatric disorders. Fast-spiking interneurons (FSIs) are sparsely distributed throughout the NAc, forming local feedforward inhibitory circuits. It remains elusive how FSI-based feedforward circuits regulate the output of NAc MSNs. Here, we investigated a distinct subpopulation of NAc FSIs that express the cannabinoid receptor type-1 (CB1)...
January 4, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27926876/potentiation-of-synaptic-glun2b-nmdar-currents-by-fyn-kinase-is-gated-through-bdnf-mediated-disinhibition-in-spinal-pain-processing
#10
Michael E Hildebrand, Jian Xu, Annemarie Dedek, Yi Li, Ameet S Sengar, Simon Beggs, Paul J Lombroso, Michael W Salter
In chronic pain states, the neurotrophin brain-derived neurotrophic factor (BDNF) transforms the output of lamina I spinal neurons by decreasing synaptic inhibition. Pain hypersensitivity also depends on N-methyl-D-aspartate receptors (NMDARs) and Src-family kinases, but the locus of NMDAR dysregulation remains unknown. Here, we show that NMDAR-mediated currents at lamina I synapses are potentiated in a peripheral nerve injury model of neuropathic pain. We find that BDNF mediates NMDAR potentiation through activation of TrkB and phosphorylation of the GluN2B subunit by the Src-family kinase Fyn...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27913590/control-of-spike-transfer-at-hippocampal-mossy-fiber-synapses-in-vivo-by-gabaa-and-gabab-receptor-mediated-inhibition
#11
Stefano Zucca, Marilena Griguoli, Meryl Malézieux, Noëlle Grosjean, Mario Carta, Christophe Mulle
: Despite extensive studies in hippocampal slices and incentive from computational theories, the synaptic mechanisms underlying information transfer at mossy fiber (mf) connections between the dentate gyrus (DG) and CA3 neurons in vivo are still elusive. Here we used an optogenetic approach in mice to selectively target and control the activity of DG granule cells (GCs) while performing whole cell and juxtacellular recordings of CA3 neurons in vivo In CA3 pyramidal cells (PCs), mf-CA3 synaptic responses consisted predominantly of an inhibitory postsynaptic potential (IPSP) at low stimulation frequency (0...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27911754/cortical-control-of-spatial-resolution-by-vip-interneurons
#12
Inbal Ayzenshtat, Mahesh Miikael Karnani, Jesse Jackson, Rafael Yuste
: Neuronal tuning, defined by the degree of selectivity to a specific stimulus, is a hallmark of cortical computation. Understanding the role of GABAergic interneurons in shaping cortical tuning is now possible with the ability to manipulate interneuron classes selectively. Here, we show that interneurons expressing vasoactive intestinal polypeptide (VIP(+)) regulate the spatial frequency (SF) tuning of pyramidal neurons in mouse visual cortex. Using two-photon calcium imaging and optogenetic manipulations of VIP(+) cell activity, we found that activating VIP(+) cells elicited a stronger network response to stimuli of higher SFs, whereas suppressing VIP(+) cells resulted in a network response shift toward lower SFs...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27909103/habenula-induced-inhibition-of-midbrain-dopamine-neurons-is-diminished-by-lesions-of-the-rostromedial-tegmental-nucleus
#13
P Leon Brown, Heather Palacorolla, Dana Brady, Katelyn Riegger, Greg I Elmer, Paul D Shepard
: Neurons in the lateral habenula (LHb) are transiently activated by aversive events and have been implicated in associative learning. Functional changes associated with tonic and phasic activation of the LHb are often attributed to a corresponding inhibition of midbrain dopamine (DA) neurons. Activation of GABAergic neurons in the rostromedial tegmental nucleus (RMTg), a region that receives dense projections from the LHb and projects strongly to midbrain monoaminergic nuclei, is believed to underlie the transient inhibition of DA neurons attributed to activation of the LHb...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27815363/stage-specific-timing-of-the-microrna-regulation-of-lin-28-by-the-heterochronic-gene-lin-14-in-caenorhabditis-elegans
#14
Jennifer Tsialikas, Mitchell A Romens, Allison Abbott, Eric G Moss
In normal development, the order and synchrony of diverse developmental events must be explicitly controlled. In the nematode Caenorhabditis elegans, the timing of larval events is regulated by hierarchy of proteins and microRNAs (miRNAs) known as the heterochronic pathway. These regulators are organized in feedforward and feedback interactions to form a robust mechanism for specifying the timing and execution of cell fates at successive stages. One member of this pathway is the RNA binding protein LIN-28, which promotes pluripotency and cell fate decisions in successive stages...
January 2017: Genetics
https://www.readbyqxmd.com/read/27796298/spontaneous-emergence-of-fast-attractor-dynamics-in-a-model-of-developing-primary-visual-cortex
#15
Thomas Miconi, Jeffrey L McKinstry, Gerald M Edelman
Recent evidence suggests that neurons in primary sensory cortex arrange into competitive groups, representing stimuli by their joint activity rather than as independent feature analysers. A possible explanation for these results is that sensory cortex implements attractor dynamics, although this proposal remains controversial. Here we report that fast attractor dynamics emerge naturally in a computational model of a patch of primary visual cortex endowed with realistic plasticity (at both feedforward and lateral synapses) and mutual inhibition...
October 31, 2016: Nature Communications
https://www.readbyqxmd.com/read/27774490/implications-of-visual-attention-phenomena-for-models-of-preferential-choice
#16
Timothy L Mullett, Neil Stewart
We use computational modeling to examine the ability of evidence accumulation models to produce the reaction time (RT) distributions and attentional biases found in behavioral and eye-tracking research. We focus on simulating RTs and attention in binary choice with particular emphasis on whether different models can predict the late onset bias (LOB), commonly found in eye movements during choice (sometimes called the gaze cascade). The first finding is that this bias is predicted by models even when attention is entirely random and independent of the choice process...
October 2016: Decision (Washington)
https://www.readbyqxmd.com/read/27741229/theta-gamma-coding-meets-communication-through-coherence-neuronal-oscillatory-multiplexing-theories-reconciled
#17
Douglas McLelland, Rufin VanRullen
Several theories have been advanced to explain how cross-frequency coupling, the interaction of neuronal oscillations at different frequencies, could enable item multiplexing in neural systems. The communication-through-coherence theory proposes that phase-matching of gamma oscillations between areas enables selective processing of a single item at a time, and a later refinement of the theory includes a theta-frequency oscillation that provides a periodic reset of the system. Alternatively, the theta-gamma neural code theory proposes that a sequence of items is processed, one per gamma cycle, and that this sequence is repeated or updated across theta cycles...
October 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27725086/an-excitatory-cortical-feedback-loop-gates-retinal-wave-transmission-in-rodent-thalamus
#18
Yasunobu Murata, Matthew T Colonnese
Spontaneous retinal waves are critical for the development of receptive fields in visual thalamus (LGN) and cortex (VC). Despite a detailed understanding of the circuit specializations in retina that generate waves, whether central circuit specializations also exist to control their propagation through visual pathways of the brain is unknown. Here we identify a developmentally transient, corticothalamic amplification of retinal drive to thalamus as a mechanism for retinal wave transmission in the infant rat brain...
October 11, 2016: ELife
https://www.readbyqxmd.com/read/27693625/a-neural-mechanism-of-dynamic-gating-of-task-relevant-information-by-top-down-influence-in-primary-visual-cortex
#19
Akikazu Kamiyama, Kazuhisa Fujita, Yoshiki Kashimori
Visual recognition involves bidirectional information flow, which consists of bottom-up information coding from retina and top-down information coding from higher visual areas. Recent studies have demonstrated the involvement of early visual areas such as primary visual area (V1) in recognition and memory formation. V1 neurons are not passive transformers of sensory inputs but work as adaptive processor, changing their function according to behavioral context. Top-down signals affect tuning property of V1 neurons and contribute to the gating of sensory information relevant to behavior...
December 2016: Bio Systems
https://www.readbyqxmd.com/read/27669144/recruitment-of-inhibition-and-excitation-across-mouse-visual-cortex-depends-on-the-hierarchy-of-interconnecting-areas
#20
Rinaldo David D'Souza, Andrew Max Meier, Pawan Bista, Quanxin Wang, Andreas Burkhalter
Diverse features of sensory stimuli are selectively processed in distinct brain areas. The relative recruitment of inhibitory and excitatory neurons within an area controls the gain of neurons for appropriate stimulus coding. We examined how such a balance of inhibition and excitation is differentially recruited across multiple levels of a cortical hierarchy by mapping the locations and strengths of synaptic inputs to pyramidal and parvalbumin (PV)-expressing neurons in feedforward and feedback pathways interconnecting primary (V1) and two higher visual areas...
September 26, 2016: ELife
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