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Cortical microcircuit

Alexandra L Petrache, Aarib Rajulawalla, Anqi Shi, Andrea Wetzel, Takashi Saito, Takaomi C Saido, Kirsten Harvey, Afia B Ali
Synaptic dysfunction is widely proposed as an initial insult leading to the neurodegeneration observed in Alzheimer's disease (AD). We hypothesize that the initial insult originates in the lateral entorhinal cortex (LEC) due to deficits in key interneuronal functions and synaptic signaling mechanisms, in particular, Wnt (Wingless/integrated). To investigate this hypothesis, we utilized the first knock-in mouse model of AD (AppNL-F/NL-F), expressing a mutant form of human amyloid-β (Aβ) precursor protein. This model shows an age-dependent accumulation of Aβ, neuroinflammation, and neurodegeneration...
February 15, 2019: Cerebral Cortex
Murat Demirtaş, Joshua B Burt, Markus Helmer, Jie Lisa Ji, Brendan D Adkinson, Matthew F Glasser, David C Van Essen, Stamatios N Sotiropoulos, Alan Anticevic, John D Murray
The large-scale organization of dynamical neural activity across cortex emerges through long-range interactions among local circuits. We hypothesized that large-scale dynamics are also shaped by heterogeneity of intrinsic local properties across cortical areas. One key axis along which microcircuit properties are specialized relates to hierarchical levels of cortical organization. We developed a large-scale dynamical circuit model of human cortex that incorporates heterogeneity of local synaptic strengths, following a hierarchical axis inferred from magnetic resonance imaging (MRI)-derived T1- to T2-weighted (T1w/T2w) mapping and fit the model using multimodal neuroimaging data...
February 5, 2019: Neuron
Tatiana B Tikhonova, Takeaki Miyamae, Yelena Gulchina, David A Lewis, Guillermo Gonzalez-Burgos
Cholinergic neuromodulation is thought to shape network activity in the PFC, and thus PFC-dependent cognitive functions. ACh may modulate the activity of parvalbumin-positive (PV+ ) neurons, which critically regulate cortical network function. However, the mechanisms of cholinergic regulation of PV+ neuron activity, and particularly of the basket cell (BC) versus chandelier cell (ChC) subtypes, are unclear. Using patch clamp recordings in acute slices, we examined the effects of the ACh receptor (AChR) agonist carbachol on the excitatory synaptic drive onto BCs or ChCs in layers 2 to 6 of mouse PFC...
September 2018: ENeuro
Scott R Pluta, Greg I Telian, Alexander Naka, Hillel Adesnik
The descending microcircuit from layer 2/3 (L2/3) to layer 5 (L5) is one of the strongest excitatory pathways in the cortex, presumably forming a core component of its feed-forward hierarchy. To date, however, no experiments have selectively tested the impact of L2/3 activity on L5 during active sensation. We employed optogenetic, cell-type specific manipulation of L2/3 neurons in the barrel cortex of actively sensing mice (of either sex) to elucidate the significance of this pathway to sensory coding in L5...
January 16, 2019: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Rammohan Shukla, Thomas D Prevot, Leon French, Ruth Isserlin, Brad R Rocco, Mounira Banasr, Gary D Bader, Etienne Sibille
BACKGROUND: Aging is accompanied by altered thinking (cognition) and feeling (mood), functions that depend on information processing by brain cortical cell microcircuits. We hypothesized that age-associated long-term functional and biological changes are mediated by gene transcriptomic changes within neuronal cell types forming cortical microcircuits, namely excitatory pyramidal cells (PYCs) and inhibitory gamma-aminobutyric acidergic neurons expressing vasoactive intestinal peptide (Vip), somatostatin (Sst), and parvalbumin (Pvalb)...
October 5, 2018: Biological Psychiatry
Kaleb A Lowe, Jeffrey D Schall
Frontal eye field (FEF) in macaque monkeys contributes to visual attention, visual-motor transformations and production of eye movements. Traditionally, neurons in FEF have been classified by the magnitude of increased discharge rates following visual stimulus presentation, during a waiting period, and associated with eye movement production. However, considerable heterogeneity remains within the traditional visual, visuomovement, and movement categories. Cluster analysis is a data-driven method of identifying self-segregating groups within a dataset...
September 2018: ENeuro
Maximilian Schmidt, Rembrandt Bakker, Kelly Shen, Gleb Bezgin, Markus Diesmann, Sacha Jennifer van Albada
Cortical activity has distinct features across scales, from the spiking statistics of individual cells to global resting-state networks. We here describe the first full-density multi-area spiking network model of cortex, using macaque visual cortex as a test system. The model represents each area by a microcircuit with area-specific architecture and features layer- and population-resolved connectivity between areas. Simulations reveal a structured asynchronous irregular ground state. In a metastable regime, the network reproduces spiking statistics from electrophysiological recordings and cortico-cortical interaction patterns in fMRI functional connectivity under resting-state conditions...
October 2018: PLoS Computational Biology
Youngsun T Cho, Norman H Lam, Martina Starc, Nicole Santamauro, Aleksandar Savic, Caroline K Diehl, Charles H Schleifer, Flora Moujaes, Vinod H Srihari, Grega Repovs, John D Murray, Alan Anticevic
Reward processing and cognition are disrupted in schizophrenia (SCZ), yet how these processes interface is unknown. In SCZ, deficits in reward representation may affect motivated, goal-directed behaviors. To test this, we examined the effects of monetary reward on spatial working memory (WM) performance in patients with SCZ. To capture complimentary effects, we tested biophysically grounded computational models of neuropharmacologic manipulations onto a canonical fronto-parietal association cortical microcircuit capable of WM computations...
October 2018: Journal of Abnormal Psychology
C Bosman, N Aldunate
Wakefulness and sleep are two qualitatively different behavioral states. The mechanisms underlying these behavioral states can be traced back to the coordinated functioning of cortical microcircuits. The stereotypical activity of cortical microcircuits during wakefulness and sleep shapes a cortical state, defined as an organized neuronal network functioning across time. Cortical microcircuits are conformed by pyramidal cells and several interneurons, organized into a six-layer structure that contains well defined connections across excitatory and inhibitory cells...
September 1, 2018: Archives Italiennes de Biologie
Vincent Magloire, Marion S Mercier, Dimitri M Kullmann, Ivan Pavlov
Seizures are complex pathological network events characterized by excessive and hypersynchronized activity of neurons, including a highly diverse population of GABAergic interneurons. Although the primary function of inhibitory interneurons under normal conditions is to restrain excitation in the brain, this system appears to fail intermittently, allowing runaway excitation. Recent developments in optogenetics, combined with genetic tools and advanced electrophysiological and imaging techniques, allow us for the first time to assess the causal roles of identified cell-types in network dynamics...
October 15, 2018: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Richard E Rosch, Sukhvir Wright, Gerald Cooray, Margarita Papadopoulou, Sushma Goyal, Ming Lim, Angela Vincent, A Louise Upton, Torsten Baldeweg, Karl J Friston
NMDA-receptor antibodies (NMDAR-Abs) cause an autoimmune encephalitis with a diverse range of EEG abnormalities. NMDAR-Abs are believed to disrupt receptor function, but how blocking this excitatory synaptic receptor can lead to paroxysmal EEG abnormalities-or even seizures-is poorly understood. Here we show that NMDAR-Abs change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity and predispose brain dynamics to paroxysmal abnormalities...
October 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
Erik Ellwardt, Gautam Pramanik, Dirk Luchtman, Tanja Novkovic, Eduardo Rosales Jubal, Johannes Vogt, Isabelle Arnoux, Christina Francisca Vogelaar, Shibajee Mandal, Melanie Schmalz, Zeke Barger, Inigo Ruiz de Azua, Tanja Kuhlmann, Beat Lutz, Thomas Mittmann, Stefan Bittner, Frauke Zipp, Albrecht Stroh
Multiple sclerosis (MS) patients exhibit neuropsychological symptoms in early disease despite the immune attack occurring predominantly in white matter and spinal cord. It is unclear why neurodegeneration may start early in the disease and is prominent in later stages. We assessed cortical microcircuit activity by employing spiking-specific two-photon Ca2+ imaging in proteolipid protein-immunized relapsing-remitting SJL/J mice in vivo. We identified the emergence of hyperactive cortical neurons in remission only, independent of direct immune-mediated damage and paralleled by elevated anxiety...
October 2018: Nature Neuroscience
Stephanie C Seeman, Luke Campagnola, Pasha A Davoudian, Alex Hoggarth, Travis A Hage, Alice Bosma-Moody, Christopher A Baker, Jung Hoon Lee, Stefan Mihalas, Corinne Teeter, Andrew L Ko, Jeffrey G Ojemann, Ryder P Gwinn, Daniel L Silbergeld, Charles Cobbs, John Phillips, Ed Lein, Gabe Murphy, Christof Koch, Hongkui Zeng, Tim Jarsky
Generating a comprehensive description of cortical networks requires a large-scale, systematic approach. To that end, we have begun a pipeline project using multipatch electrophysiology, supplemented with two-photon optogenetics, to characterize connectivity and synaptic signaling between classes of neurons in adult mouse primary visual cortex (V1) and human cortex. We focus on producing results detailed enough for the generation of computational models and enabling comparison with future studies. Here, we report our examination of intralaminar connectivity within each of several classes of excitatory neurons...
September 26, 2018: ELife
Arabinda Mishra, Shantanu Majumdar, Feng Wang, George H Wilson, John C Gore, Li Min Chen
Whereas resting state blood oxygenation-level dependent (BOLD) functional MRI has been widely used to assess functional connectivity between cortical regions, the laminar specificity of such measures is poorly understood. This study aims to determine: (a) whether the resting state functional connectivity (rsFC) between two functionally related cortical regions varies with cortical depth, (b) the relationship between layer-resolved tactile stimulus-evoked activation pattern and interlayer rsFC pattern between two functionally distinct but related somatosensory areas 3b and 1, and (c) the effects of spatial resolution on rsFC measures...
September 25, 2018: Human Brain Mapping
Franco Ortiz, W P Karel Zapfe, Andreas Draguhn, Rafael Gutiérrez
Fast ripples (FRs; activity of >250 Hz) have been considered as a biomarker of epileptic activity in the hippocampus and entorhinal cortex; it is thought that they signal the focus of seizure generation. Similar high-frequency network activity has been produced in vitro by changing extracellular medium composition, by using pro-epileptic substances, or by electrical stimulation. Here we study the propagation of these events between different subregions of the male rat hippocampus in a recently introduced experimental model of FRs in entorhinal cortex-hippocampal slices in vitro By using a matrix of 4096 microelectrodes, the sites of initiation, propagation pathways, and spatiotemporal characteristics of activity patterns could be studied with unprecedented high resolution...
October 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Isabelle Arnoux, Michael Willam, Nadine Griesche, Jennifer Krummeich, Hirofumi Watari, Nina Offermann, Stephanie Weber, Partha Narayan Dey, Changwei Chen, Olivia Monteiro, Sven Buettner, Katharina Meyer, Daniele Bano, Konstantin Radyushkin, Rosamund Langston, Jeremy J Lambert, Erich Wanker, Axel Methner, Sybille Krauss, Susann Schweiger, Albrecht Stroh
Catching primal functional changes in early, 'very far from disease onset' (VFDO) stages of Huntington's disease is likely to be the key to a successful therapy. Focusing on VFDO stages, we assessed neuronal microcircuits in premanifest Hdh150 knock-in mice. Employing in vivo two-photon Ca2+ imaging, we revealed an early pattern of circuit dysregulation in the visual cortex - one of the first regions affected in premanifest Huntington's disease - characterized by an increase in activity, an enhanced synchronicity and hyperactive neurons...
September 4, 2018: ELife
Vafa Andalibi, Henri Hokkanen, Simo Vanni
Simulation of the cerebral cortex requires a combination of extensive domain-specific knowledge and efficient software. However, when the complexity of the biological system is combined with that of the software, the likelihood of coding errors increases, which slows model adjustments. Moreover, few life scientists are familiar with software engineering and would benefit from simplicity in form of a high-level abstraction of the biological model. Our primary aim was to build a scalable cortical simulation framework for personal computers...
August 27, 2018: Neural Computation
Richard E Rosch, Ryszard Auksztulewicz, Pui Duen Leung, Karl J Friston, Torsten Baldeweg
BACKGROUND: Disturbances in N-methyl-D-aspartate receptors (NMDARs)-as implicated in patients with schizophrenia-can cause regionally specific electrophysiological effects. Both animal models of NMDAR blockade and clinical studies in patients with schizophrenia have suggested that behavioral phenotypes are associated with reduction in inhibition within the frontal cortex. METHODS: Here we investigate event-related potentials to a roving auditory oddball paradigm under ketamine in healthy human volunteers (N= 18; double-blind, placebo-controlled, crossover design)...
August 13, 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Joshua B Burt, Murat Demirtaş, William J Eckner, Natasha M Navejar, Jie Lisa Ji, William J Martin, Alberto Bernacchia, Alan Anticevic, John D Murray
Hierarchy provides a unifying principle for the macroscale organization of anatomical and functional properties across primate cortex, yet microscale bases of specialization across human cortex are poorly understood. Anatomical hierarchy is conventionally informed by invasive tract-tracing measurements, creating a need for a principled proxy measure in humans. Moreover, cortex exhibits marked interareal variation in gene expression, yet organizing principles of cortical transcription remain unclear. We hypothesized that specialization of cortical microcircuitry involves hierarchical gradients of gene expression...
September 2018: Nature Neuroscience
Ashok S Chauhan, Joseph D Taylor, Alain Nogaret
During cognitive tasks cortical microcircuits synchronize to bind stimuli into unified perception. The emergence of coherent rhythmic activity is thought to be inhibition-driven and stimulation-dependent. However, the exact mechanisms of synchronization remain unknown. Recent optogenetic experiments have identified two neuron sub-types as the likely inhibitory vectors of synchronization. Here, we show that local networks mimicking the soma-targeting properties observed in fast-spiking interneurons and the dendrite-projecting properties observed in somatostatin interneurons synchronize through different mechanisms which may provide adaptive advantages by combining flexibility and robustness...
July 30, 2018: Scientific Reports
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