scholarly journals Extreme stiffness of neuronal synapses and implications for synaptic adhesion and plasticity

2020 ◽  
Author(s):  
Ju Yang ◽  
Nicola Mandriota ◽  
Steven Glenn Harrellson ◽  
John Anthony Jones-Molina ◽  
Rafael Yuste ◽  
...  
Keyword(s):  
Structural Changes ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Critical Role ◽  
Theoretical Models ◽  
Cell Types ◽  
Long Term Potentiation ◽  
Biophysical Model ◽  
And Function ◽  
Circuit Function

AbstractSynapses play a critical role in neural circuits, and they are potential sites for learning and memory. Maintenance of synaptic adhesion is critical for neural circuit function, however, biophysical mechanisms that help maintain synaptic adhesion are not clear. Studies with various cell types demonstrated the important role of stiffness in cellular adhesions. Although synaptic stiffness could also play a role in synaptic adhesion, stiffnesses of synapses are difficult to characterize due to their small size and challenges in verifying synapse identity and function. To address these challenges, we have developed an experimental platform that combines atomic force microscopy, fluorescence microscopy, and transmission electron microscopy. Here, using this platform, we report that functional, mature, excitatory synapses had an average elastic modulus of approximately 200 kPa, two orders of magnitude larger than that of the brain tissue, suggesting stiffness might have a role in synapse function. Similar to various functional and anatomical features of neural circuits, synaptic stiffness had a lognormal-like distribution, hinting a possible regulation of stiffness by processes involved in neural circuit function. In further support of this possibility, we observed that synaptic stiffness was correlated with spine size, a quantity known to correlate with synaptic strength. Using established stages of the long-term potentiation timeline and theoretical models of adhesion cluster dynamics, we developed a biophysical model of the synapse that not only explains extreme stiffness of synapses, their statistical distribution, and correlation with spine size, but also offers an explanation to how early biomolecular and structural changes during functional potentiation could lead to strengthening of synaptic adhesion. According to this model, synaptic stiffness serves as an indispensable physical messenger, feeding information back to synaptic adhesion molecules to facilitate maintenance of synaptic adhesion.

scholarly journals A genetic, genomic, and computational resource for exploring neural circuit function

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Fred P Davis ◽  
Aljoscha Nern ◽  
Serge Picard ◽  
Michael B Reiser ◽  
Gerald M Rubin ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Neural Circuit ◽  
Individual Cell ◽  
Probabilistic Method ◽  
Expression Patterns ◽  
Cell Types ◽  
Receptor Expression ◽  
Generating Functional ◽  
Circuit Function ◽  
Different Cell Types

The anatomy of many neural circuits is being characterized with increasing resolution, but their molecular properties remain mostly unknown. Here, we characterize gene expression patterns in distinct neural cell types of the Drosophila visual system using genetic lines to access individual cell types, the TAPIN-seq method to measure their transcriptomes, and a probabilistic method to interpret these measurements. We used these tools to build a resource of high-resolution transcriptomes for 100 driver lines covering 67 cell types, available at http://www.opticlobe.com. Combining these transcriptomes with recently reported connectomes helps characterize how information is transmitted and processed across a range of scales, from individual synapses to circuit pathways. We describe examples that include identifying neurotransmitters, including cases of apparent co-release, generating functional hypotheses based on receptor expression, as well as identifying strong commonalities between different cell types.

scholarly journals Zebrafish Dscaml1 is Essential for Retinal Patterning and Function of Oculomotor Subcircuits

2019 ◽  
Author(s):  
Manxiu Ma ◽  
Alexandro D. Ramirez ◽  
Tong Wang ◽  
Rachel L. Roberts ◽  
Katherine E. Harmon ◽  
...  
Keyword(s):  
Animal Model ◽  
Light Adaptation ◽  
Neural Circuit ◽  
Oculomotor System ◽  
Gaze Stabilization ◽  
Ocular Disorders ◽  
Motor Apraxia ◽  
Premotor Pathways ◽  
And Function ◽  
Circuit Function

AbstractDown Syndrome Cell Adhesion Molecules (dscam and dscaml1) are essential regulators of neural circuit assembly, but their roles in vertebrate neural circuit function are still mostly unexplored. We investigated the role of dscaml1 in the zebrafish oculomotor system, where behavior, circuit function, and neuronal activity can be precisely quantified. Loss of zebrafish dscaml1 resulted in deficits in retinal patterning and light adaptation, consistent with its known roles in mammals. Oculomotor analyses showed that mutants have abnormal gaze stabilization, impaired fixation, disconjugation, and faster fatigue. Notably, the saccade and fatigue phenotypes in dscaml1 mutants are reminiscent of human ocular motor apraxia, for which no animal model exists. Two-photon calcium imaging showed that loss of dscaml1 leads to impairment in the saccadic premotor pathway but not the pretectum-vestibular premotor pathway, indicating a subcircuit requirement for dscaml1. Together, we show that dscaml1 has both broad and specific roles in oculomotor circuit function, providing a new animal model to investigate the development of premotor pathways and their associated human ocular disorders.

Form and Function in Cells of the Brain

The Neuron ◽  
2015 ◽  
pp. 23-38
Author(s):  
Irwin B. Levitan ◽  
Leonard K. Kaczmarek
Keyword(s):  
Axonal Transport ◽  
Molecular Motors ◽  
Critical Role ◽  
Neuronal Cell ◽  
Cell Types ◽  
Neuronal Cell Body ◽  
Long Distance ◽  
Form And Function ◽  
And Function ◽  
The Brain

This chapter examines unique mechanisms that the neuron has evolved to establish and maintain the form required for its specialized signaling functions. Unlike some other organs, the brain contains a variety of cell types including several classes of glial cells, which play a critical role in the formation of the myelin sheath around axons and may be involved in immune responses, synaptic transmission, and long-distance calcium signaling in the brain. Neurons share many features in common with other cells (including glia), but they are distinguished by their highly asymmetrical shapes. The neuronal cytoskeleton is essential for establishing this cell shape during development and for maintaining it in adulthood. The process of axonal transport moves vesicles and other organelles to regions remote from the neuronal cell body. Proteins such as kinesin and dynein, called molecular motors, make use of the energy released by hydrolysis of ATP to drive axonal transport.

scholarly journals The dialectic of Hebb and homeostasis

2017 ◽  
Vol 372 (1715) ◽  
pp. 20160258 ◽  
Author(s):  
Gina G. Turrigiano
Keyword(s):  
Recent Progress ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Homeostatic Plasticity ◽  
Homeostatic Control ◽  
Spatial And Temporal Scales ◽  
Network Function ◽  
Hebbian Plasticity ◽  
Circuit Function ◽  
Hebbian Mechanisms

It has become widely accepted that homeostatic and Hebbian plasticity mechanisms work hand in glove to refine neural circuit function. Nonetheless, our understanding of how these fundamentally distinct forms of plasticity compliment (and under some circumstances interfere with) each other remains rudimentary. Here, I describe some of the recent progress of the field, as well as some of the deep puzzles that remain. These include unravelling the spatial and temporal scales of different homeostatic and Hebbian mechanisms, determining which aspects of network function are under homeostatic control, and understanding when and how homeostatic and Hebbian mechanisms must be segregated within neural circuits to prevent interference. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.

scholarly journals The Many Forms and Functions of Long Term Plasticity at GABAergic Synapses

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Arianna Maffei
Keyword(s):  
Synaptic Plasticity ◽  
Neural Circuits ◽  
Dynamic Range ◽  
Theoretical Work ◽  
Long Term Potentiation ◽  
Inhibitory Neurons ◽  
Gabaergic Synapses ◽  
The Many ◽  
And Function

On February 12th 1973, Bliss and Lomo submitted their findings on activity-dependent plasticity of glutamatergic synapses. After this groundbreaking discovery, long-term potentiation (LTP) and depression (LTD) gained center stage in the study of learning, memory, and experience-dependent refinement of neural circuits. While LTP and LTD are extensively studied and their relevance to brain function is widely accepted, new experimental and theoretical work recently demonstrates that brain development and function relies on additional forms of plasticity, some of which occur at nonglutamatergic synapses. The strength of GABAergic synapses is modulated by activity, and new functions for inhibitory synaptic plasticity are emerging. Together with excitatory neurons, inhibitory neurons shape the excitability and dynamic range of neural circuits. Thus, the understanding of inhibitory synaptic plasticity is crucial to fully comprehend the physiology of brain circuits. Here, I will review recent findings about plasticity at GABAergic synapses and discuss how it may contribute to circuit function.

scholarly journals Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor

2004 ◽  
Vol 167 (2) ◽  
pp. 293-302 ◽  
Author(s):  
Fubito Nakatsu ◽  
Motohiro Okada ◽  
Fumiaki Mori ◽  
Noriko Kumazawa ◽  
Hiroto Iwasa ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Neuronal Excitability ◽  
Critical Role ◽  
Physiological Role ◽  
Adaptor Protein ◽  
Epileptic Seizures ◽  
Gaba Release ◽  
Long Term Potentiation ◽  
Clathrin Adaptor ◽  
And Function

AP-3 is a member of the adaptor protein (AP) complex family that regulates the vesicular transport of cargo proteins in the secretory and endocytic pathways. There are two isoforms of AP-3: the ubiquitously expressed AP-3A and the neuron-specific AP-3B. Although the physiological role of AP-3A has recently been elucidated, that of AP-3B remains unsolved. To address this question, we generated mice lacking μ3B, a subunit of AP-3B. μ3B−/− mice suffered from spontaneous epileptic seizures. Morphological abnormalities were observed at synapses in these mice. Biochemical studies demonstrated the impairment of γ-aminobutyric acid (GABA) release because of, at least in part, the reduction of vesicular GABA transporter in μ3B−/− mice. This facilitated the induction of long-term potentiation in the hippocampus and the abnormal propagation of neuronal excitability via the temporoammonic pathway. Thus, AP-3B plays a critical role in the normal formation and function of a subset of synaptic vesicles. This work adds a new aspect to the pathogenesis of epilepsy.

scholarly journals Hypoxia. 4. Hypoxia and ion channel function

2011 ◽  
Vol 300 (5) ◽  
pp. C951-C967 ◽  
Author(s):  
Larissa A. Shimoda ◽  
Jan Polak
Keyword(s):  
Ion Channels ◽  
Cell Function ◽  
Critical Role ◽  
Cardiac Contractility ◽  
Cell Types ◽  
Cellular Processes ◽  
Oxygen Sensitive ◽  
Sense And Respond ◽  
And Function ◽  
And Control

The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes.

scholarly journals Neural architecture: from cells to circuits

2018 ◽  
Vol 120 (2) ◽  
pp. 854-866 ◽  
Author(s):  
Sarah E. V. Richards ◽  
Stephen D. Van Hooser
Keyword(s):  
Nervous System ◽  
Cerebral Cortex ◽  
Structure Function ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Neuronal Morphology ◽  
Neural Architecture ◽  
Synaptic Interactions ◽  
Branching Patterns ◽  
Circuit Function

Circuit operations are determined jointly by the properties of the circuit elements and the properties of the connections among these elements. In the nervous system, neurons exhibit diverse morphologies and branching patterns, allowing rich compartmentalization within individual cells and complex synaptic interactions among groups of cells. In this review, we summarize work detailing how neuronal morphology impacts neural circuit function. In particular, we consider example neurons in the retina, cerebral cortex, and the stomatogastric ganglion of crustaceans. We also explore molecular coregulators of morphology and circuit function to begin bridging the gap between molecular and systems approaches. By identifying motifs in different systems, we move closer to understanding the structure-function relationships that are present in neural circuits.

scholarly journals GM-CSF: Orchestrating the Pulmonary Response to Infection

2022 ◽  
Vol 12 ◽  
Author(s):  
Thomas S. McCormick ◽  
Rana B. Hejal ◽  
Luis O. Leal ◽  
Mahmoud A. Ghannoum
Keyword(s):  
Infectious Diseases ◽  
Respiratory Infections ◽  
Critical Role ◽  
Alveolar Epithelium ◽  
Cell Types ◽  
Adjunctive Treatment ◽  
Gm Csf ◽  
Lung Physiology ◽  
Pulmonary Immune System ◽  
And Function

This review summarizes the structure and function of the alveolar unit, comprised of alveolar macrophage and epithelial cell types that work in tandem to respond to infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) helps to maintain the alveolar epithelium and pulmonary immune system under physiological conditions and plays a critical role in restoring homeostasis under pathologic conditions, including infection. Given the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global spread of coronavirus disease 2019 (COVID-19), with subsequent acute respiratory distress syndrome, understanding basic lung physiology in infectious diseases is especially warranted. This review summarizes clinical and preclinical data for GM-CSF in respiratory infections, and the rationale for sargramostim (yeast-derived recombinant human [rhu] GM-CSF) as adjunctive treatment for COVID-19 and other pulmonary infectious diseases.

scholarly journals A genetic, genomic, and computational resource for exploring neural circuit function

2018 ◽  
Author(s):  
Fred P. Davis ◽  
Aljoscha Nern ◽  
Serge Picard ◽  
Michael B. Reiser ◽  
Gerald M. Rubin ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Affinity Purification ◽  
Probabilistic Method ◽  
Expression Patterns ◽  
Cell Types ◽  
Receptor Expression ◽  
List Type ◽  
Visual Neurons ◽  
Circuit Function ◽  
Different Cell Types

AbstractThe anatomy of many neural circuits is being characterized with increasing resolution, but their molecular properties remain mostly unknown. Here, we characterize gene expression patterns in distinct neural cell types of the Drosophila visual system using genetic lines to access individual cell types, the TAPIN-seq method to measure their transcriptomes, and a probabilistic method to interpret these measurements. We used these tools to build a resource of high-resolution transcriptomes for 100 driver lines covering 67 cell types, available at http://www.opticlobe.com. Combining these transcriptomes with recently reported connectomes helps characterize how information is transmitted and processed across a range of scales, from individual synapses to circuit pathways. We describe examples that include identifying neurotransmitters, including cases of co-release, generating functional hypotheses based on receptor expression, as well as identifying strong commonalities between different cell types.HighlightsTranscriptomes reveal transmitters and receptors expressed in Drosophila visual neuronsTandem affinity purification of intact nuclei (TAPIN) enables neuronal genomicsTAPIN-seq and genetic drivers establish transcriptomes of 67 Drosophila cell typesProbabilistic modeling simplifies interpretation of large transcriptome catalogs

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