scholarly journals A spatially dynamic network underlies the generation of inspiratory behaviors

2019 ◽  
Vol 116 (15) ◽  
pp. 7493-7502 ◽  
Author(s):  
Nathan A. Baertsch ◽  
Liza J. Severs ◽  
Tatiana M. Anderson ◽  
Jan-Marino Ramirez
Keyword(s):  
Network Architecture ◽  
Sensory Feedback ◽  
Behavioral Flexibility ◽  
Dynamic Network ◽  
Active Network ◽  
Intrinsic Properties ◽  
Inhibitory Network ◽  
Inspiratory Phase

The ability of neuronal networks to reconfigure is a key property underlying behavioral flexibility. Networks with recurrent topology are particularly prone to reconfiguration through changes in synaptic and intrinsic properties. Here, we explore spatial reconfiguration in the reticular networks of the medulla that generate breathing. Combined results from in vitro and in vivo approaches demonstrate that the network architecture underlying generation of the inspiratory phase of breathing is not static but can be spatially redistributed by shifts in the balance of excitatory and inhibitory network influences. These shifts in excitation/inhibition allow the size of the active network to expand and contract along a rostrocaudal medullary column during behavioral or metabolic challenges to breathing, such as changes in sensory feedback, sighing, and gasping. We postulate that the ability of this rhythm-generating network to spatially reconfigure contributes to the remarkable robustness and flexibility of breathing.

scholarly journals Myelin-specific proteins and glycolipids in rat Schwann cells and oligodendrocytes in culture.

1980 ◽  
Vol 84 (3) ◽  
pp. 483-494 ◽  
Author(s):  
R Mirsky ◽  
J Winter ◽  
E R Abney ◽  
R M Pruss ◽  
J Gavrilovic ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Schwann Cells ◽  
Dorsal Root ◽  
Basic Protein ◽  
Intrinsic Properties ◽  
Short Term ◽  
Explant Cultures ◽  
Specific Proteins

We have used antibodies to identify Schwann cells and oligodendrocytes and to study the expression of myelin-specific glycolipids and proteins in these cells isolated from perinatal rats. Our findings suggest that only Schwann cells which have been induced to myelinate make detectable amounts of galactocerebroside (GC), sulfatide, myelin basic protein (BP), or the major peripheral myelin glycoprotein (P0). When rat Schwann cells were cultured, they stopped making detectable amounts of these myelin molecules, even when the cells were associated with neurites in short-term explant cultures of dorsal root ganglion. In contrast, oligodendrocytes in dissociated cell cultures of neonatal optic nerve, corpus callosum, or cerebellum continued to make GC, sulfatide and BP for many weeks, even in the absence of neurons. These findings suggest that while rat Schwann cells require a continuing signal from appropriate axons to make detectable amounts of myelin-specific glycolipids and proteins, oligodendrocytes do not. Schwann cells and oligodendrocytes also displayed very different morphologies in vitro which appeared to reflect their known differences in myelinating properties in vivo. Since these characteristic morphologies are maintained when Schwann cells and oligodendrocytes were grown together in mixed cultures and in the absence of neurons, we concluded that they are intrinsic properties of these two different myelin-forming cells.

scholarly journals Convolutional models of RNA energetics

2018 ◽  
Author(s):  
Michelle J. Wu
Keyword(s):  
Nucleic Acid ◽  
Network Architecture ◽  
Nearest Neighbor ◽  
Current Model ◽  
Mrna Translation ◽  
Large Space ◽  
Dna And Rna ◽  
Nucleic Acid Interactions

AbstractNucleic acid molecular biology and synthetic biology are undergoing rapid advances with the emergence of designer riboswitches controlling living cells, CRISPR/Cas9-based genome editing, high-throughput RNA-based silencing, and reengineering of mRNA translation. Many of these efforts require the design of nucleic acid interactions, which relies on accurate models for DNA and RNA energetics. Existing models utilize nearest neighbor rules, which were parameterized through careful optical melting measurements. However, these relatively simple rules often fail to quantitatively account for the biophysical behavior of molecules even in vitro, let alone in vivo. This is due to the limited experimental throughput of optical melting experiments and the infinitely large space of possible motifs that can be formed. Here, we present a convolutional neural network architecture to model the energies of nucleic acid motifs, allowing for learning of representations of physical interactions that generalize to arbitrary unmeasured motifs. First, we used existing parameterizations of motif energies to train the model and demonstrate that our model is expressive enough to recapitulate the current model. Then, through training on optical melting datasets from the literature, we have shown that the model can accurately predict the thermodynamics of hairpins containing unmeasured motifs. This work demonstrates the utility of convolutional models for capturing the thermodynamic parameters that underlie nucleic acid interactions.

scholarly journals Modeling implicates inhibitory network bistability as an underpinning of seizure initiation

2019 ◽  
Author(s):  
Scott Rich ◽  
Homeira Moradi Chameh ◽  
Marjan Rafiee ◽  
Katie Ferguson ◽  
Frances K. Skinner ◽  
...  
Keyword(s):  
Brain Activity ◽  
Sudden Change ◽  
Synaptic Activity ◽  
Computational Techniques ◽  
Inhibitory Interneurons ◽  
Normal Brain ◽  
Inhibitory Network ◽  
Inhibitory Networks

AbstractA plethora of recent experimental literature implicates the abrupt, synchronous activation of GABAergic interneurons in driving the sudden change in brain activity that heralds seizure initiation. However, the mechanisms predisposing an inhibitory network toward sudden coherence specifically during ictogenesis remain unknown. We address this question by comparing simulated inhibitory networks containing control interneurons and networks containing hyper-excitable interneurons modeled to mimic treatment with 4-Aminopyridine (4-AP), an agent commonly used to model seizuresin vivoandin vitro. Ourin silicostudy demonstrates that model inhibitory networks with 4-AP interneurons are more prone than their control counterparts to exist in a bistable state in which asynchronously firing networks can abruptly transition into synchrony due to a brief perturbation. We further show that perturbations driving this transition could reasonably arisein vivobased on models of background excitatory synaptic activity in the cortex. Thus, these results propose a mechanism by which an inhibitory network can transition from incoherent to coherent dynamics in a fashion that may precipitate seizure as a downstream effect. Moreover, this mechanism specifically explains why inhibitory networks containing hyper-excitable interneurons are more vulnerable to this state change, and how such networks can undergo this transition without a permanent change in the drive to the system. This, in turn, potentially explains such networks’ increased vulnerability to seizure initiated by GABAergic activity.Author summaryFor decades, the study of epilepsy has focused on the hypothesis that over-excitation or dis-inhibition of pyramidal neurons underlies the transition from normal brain activity to seizure. However, a variety of recent experimental findings have implicated a sudden synchronous burst of activity amongst inhibitory interneurons in driving this transition. Given the counter-intuitive nature of these findings and the correspondingly novel hypothesis of seizure generation, the articulation of a feasible mechanism of action underlying this dynamic is of paramount importance for this theory’s viability. Here, we use computational techniques, particularly the concept of bistability in the context of dynamical systems, to propose a mechanism for the necessary first step in such a process: the sudden synchronization of a network of inhibitory interneurons. This is the first detailed proposal of a computational mechanism explaining any aspect of this hypothesis of which we are aware. By articulating a mechanism that not only underlies this transition, but does so in a fashion explaining why ictogenic networks might be more prone to this behavior, we provide critical support for this novel hypothesis of seizure generation and potential insight into the larger question of why individuals with epilepsy are particularly vulnerable to seizure.

scholarly journals Structure of the endocytic adaptor complex reveals the basis for efficient membrane anchoring during clathrin-mediated endocytosis

2020 ◽  
Author(s):  
Javier Lizarrondo ◽  
David P. Klebl ◽  
Stephan Niebling ◽  
Marc Abella ◽  
Martin A. Schroer ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Complex Formation ◽  
Dynamic Network ◽  
Time Resolved ◽  
Binding Domains ◽  
Membrane Invagination ◽  
Protein Membrane ◽  
Membrane Anchoring

AbstractDuring clathrin-mediated endocytosis, a complex and dynamic network of protein-membrane interactions cooperate to achieve membrane invagination. Throughout this process, middle coat adaptors, Sla2 and Ent1, must remain attached to the plasma membrane to transmit force from the actin cytoskeleton required for successful membrane invagination. Here, we present a cryoEM structure of a 16-mer complex of membrane binding domains from Sla2 and Ent1 that anchors to the plasma membrane. Detailed mutagenesis in vitro and in vivo of the tetramer interfaces delineate the key interactions for complex formation and deficient cell growth phenotypes demonstrate the biological relevance of these interactions. Finally, time-resolved experiments in solution suggest that adaptors have evolved to achieve a fast subsecond timescale assembly in the presence of PIP2. Together, these findings provide a molecular understanding of an essential piece for the molecular puzzle of clathrin-coated sites.

scholarly journals Perfused Platforms to Mimic Bone Microenvironment at the Macro/Milli/Microscale: Pros and Cons

2022 ◽  
Vol 9 ◽  
Author(s):  
Maria Veronica Lipreri ◽  
Nicola Baldini ◽  
Gabriela Graziani ◽  
Sofia Avnet
Keyword(s):  
Extracellular Matrix ◽  
Bone Structure ◽  
Dynamic Network ◽  
Cell Types ◽  
New Drugs ◽  
Culture Methods ◽  
Increased Risk ◽  
Multiple Cell

As life expectancy increases, the population experiences progressive ageing. Ageing, in turn, is connected to an increase in bone-related diseases (i.e., osteoporosis and increased risk of fractures). Hence, the search for new approaches to study the occurrence of bone-related diseases and to develop new drugs for their prevention and treatment becomes more pressing. However, to date, a reliable in vitro model that can fully recapitulate the characteristics of bone tissue, either in physiological or altered conditions, is not available. Indeed, current methods for modelling normal and pathological bone are poor predictors of treatment outcomes in humans, as they fail to mimic the in vivo cellular microenvironment and tissue complexity. Bone, in fact, is a dynamic network including differently specialized cells and the extracellular matrix, constantly subjected to external and internal stimuli. To this regard, perfused vascularized models are a novel field of investigation that can offer a new technological approach to overcome the limitations of traditional cell culture methods. It allows the combination of perfusion, mechanical and biochemical stimuli, biological cues, biomaterials (mimicking the extracellular matrix of bone), and multiple cell types. This review will discuss macro, milli, and microscale perfused devices designed to model bone structure and microenvironment, focusing on the role of perfusion and encompassing different degrees of complexity. These devices are a very first, though promising, step for the development of 3D in vitro platforms for preclinical screening of novel anabolic or anti-catabolic therapeutic approaches to improve bone health.

scholarly journals Methods and Limits for Micro Scale Blood Vessel Flow Imaging in Scattering Media by Optical Feedback Interferometry: Application to Human Skin

Sensors ◽  
2021 ◽  
Vol 21 (4) ◽  
pp. 1300 ◽  
Author(s):  
Adam Quotb ◽  
Reza Atashkhooei ◽  
Simone Magaletti ◽  
Francis Jayat ◽  
Clement Tronche ◽  
...  
Keyword(s):  
Blood Flow ◽  
Human Skin ◽  
Network Architecture ◽  
Health Management ◽  
Optical Feedback ◽  
Flow Imaging ◽  
Scattering Media ◽  
In Vivo Test

At the micrometric scale, vessels or skin capillaries network architecture can provide useful information for human health management. In this paper, from simulation to in vitro, we investigate some limits and interests of optical feedback interferometry (OFI) for blood flow imaging of skin vascularization. In order to analyze the tissue scattering effect on OFI performances, a series of skin-tissue simulating optical phantoms have been designed, fabricated and characterized. The horizontal (2D) and vertical (depth penetration) sensing resolution of the OFI sensor have been estimated. The experimental results that we present on this study are showing a very good accordance with theoretical models. In the case of a skin phantom of 0.5 mm depth with a scattering coefficient from 0 to 10.8 mm−1, the presented OFI system is able to distinguish a pair of micro fluidic channels (100 µm × 100 µm) spaced by 10 µm. Eventually, an in vivo test on human skin is presented and, for the first time using an OFI sensor, a 2D blood flow image of a vein located just beneath the skin is computed.

scholarly journals Windup of Nociceptive Flexion Reflex Depends on Synaptic and Intrinsic Properties of Dorsal Horn Neurons in Adult Rat

2019 ◽  
Author(s):  
Franck Aby ◽  
Rabia Bouali-Benazzouz ◽  
Marc Landry ◽  
Pascal Fossat
Keyword(s):  
Spinal Cord ◽  
Progressive Increase ◽  
Ventral Horn ◽  
Intrinsic Properties ◽  
Calcium Dependent ◽  
Adult Rat ◽  
Dorsal Horn Neurons ◽  
Nociceptive Flexion Reflex

Windup, a progressive increase in spinal response to repetitive stimulations of nociceptive peripheral fibres, is a useful model to study central sensitization to pain. Windup is expressed by neurons in of both dorsal and ventral horn of the spinal cord. In juvenile rats, it has been demonstrated both in vivo and in vitro that windup depends on calcium-dependent intrinsic properties and their modulation by synaptic components. However, the involvement of these two components in the adult remain controversial. In the present study, by means of electromyographic and extracellular recordings, we show that windup in adult, in vivo, depends on a synaptic balance between excitatory NMDA receptors and inhibitory glycinergic receptors. We also demonstrate the involvement of L-type calcium channels in both the dorsal and ventral horn of the spinal cord. These results indicate that windup in adults is similar to juveniles rats and that windup properties are the same regardless spinal network, i.e. sensory or motor.

scholarly journals Pairwise Assembly Determines the Intrinsic Potential for Self-Organization and Mechanical Properties of Keratin Filaments

2002 ◽  
Vol 13 (1) ◽  
pp. 382-391 ◽  
Author(s):  
Soichiro Yamada ◽  
Denis Wirtz ◽  
Pierre A. Coulombe
Keyword(s):  
Mechanical Properties ◽  
Polymer Concentration ◽  
Structural Proteins ◽  
Self Organization ◽  
Type I ◽  
Intrinsic Properties ◽  
Relative Paucity ◽  
Keratin Filaments

Most type I and II keratin genes are spatially and temporally regulated in a pairwise manner in epithelial tissues, where they represent the major structural proteins. Epithelia can be partitioned into simple (single-layered) and complex (multilayered) types. We compared the structural and mechanical properties of natural keratin polymers occurring in complex (K5-K14) and simple (K8-K18) epithelia. The intrinsic properties of these distantly related keratin filaments, whether dispersed or bundled in vitro, were surprisingly similar in all respects when at high polymer concentration. When type I and II assembly partners were switched to give rise to mismatched polymers (K5-K18; K8-K14), the interfilament interactions, which determine the structural and mechanical properties of keratin polymers, were significantly altered. We also show that a K5-K16 polymer exhibits lesser elasticity than K5- K14, which may help explain the inability of K16 to fully rescue the skin blistering characteristic of K14 null mice. The property of self-interaction exhibited by keratin filaments is likely to assist their function in vivo and may account for the relative paucity of cytoplasmic and keratin-specific cross-linkers. Our findings underscore the fundamental importance of pairwise polymerization and have implications for the functional significance of keratin sequence diversity.

scholarly journals Windup of Nociceptive Flexion Reflex Depends on Synaptic and Intrinsic Properties of Dorsal Horn Neurons in Adult Rats

2019 ◽  
Vol 20 (24) ◽  
pp. 6146
Author(s):  
Franck Aby ◽  
Rabia Bouali-Benazzouz ◽  
Marc Landry ◽  
Pascal Fossat
Keyword(s):  
Spinal Cord ◽  
Progressive Increase ◽  
Ventral Horn ◽  
Intrinsic Properties ◽  
Adult Rats ◽  
Juvenile Rats ◽  
Calcium Dependent ◽  
Nociceptive Flexion Reflex

Windup, a progressive increase in spinal response to repetitive stimulations of nociceptive peripheral fibers, is a useful model to study central sensitization to pain. Windup is expressed by neurons in both the dorsal and ventral horn of the spinal cord. In juvenile rats, it has been demonstrated both in vivo and in vitro that windup depends on calcium-dependent intrinsic properties and their modulation by synaptic components. However, the involvement of these two components in the adults remains controversial. In the present study, by means of electromyographic and extracellular recordings, we show that windup in adults, in vivo, depends on a synaptic balance between excitatory N-methyl-D-aspartate (NMDA) receptors and inhibitory glycinergic receptors. We also demonstrate the involvement of L-type calcium channels in both the dorsal and ventral horn of the spinal cord. These results indicate that windup in adults is similar to juvenile rats and that windup properties are the same regardless of the spinal network, i.e., sensory or motor.

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