scholarly journals A genetic basis for molecular asymmetry at vertebrate electrical synapses

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Adam C Miller ◽  
Alex C Whitebirch ◽  
Arish N Shah ◽  
Kurt C Marsden ◽  
Michael Granato ◽  
...  
Keyword(s):  
Gap Junction ◽  
Genetic Basis ◽  
Behavioral Performance ◽  
Electrical Synapses ◽  
Network Function ◽  
Molecular Asymmetry ◽  
Metabolic Coupling ◽  
Neuronal Synapses ◽  
Chemical Synapses ◽  
And Function

Neural network function is based upon the patterns and types of connections made between neurons. Neuronal synapses are adhesions specialized for communication and they come in two types, chemical and electrical. Communication at chemical synapses occurs via neurotransmitter release whereas electrical synapses utilize gap junctions for direct ionic and metabolic coupling. Electrical synapses are often viewed as symmetrical structures, with the same components making both sides of the gap junction. By contrast, we show that a broad set of electrical synapses in zebrafish, Danio rerio, require two gap-junction-forming Connexins for formation and function. We find that one Connexin functions presynaptically while the other functions postsynaptically in forming the channels. We also show that these synapses are required for the speed and coordination of escape responses. Our data identify a genetic basis for molecular asymmetry at vertebrate electrical synapses and show they are required for appropriate behavioral performance.

scholarly journals A genetic basis for molecular asymmetry at vertebrate electrical synapses

2017 ◽  
Author(s):  
Adam C Miller ◽  
Alex C Whitebirch ◽  
Arish N Shah ◽  
Kurt C Marsden ◽  
Michael Granato ◽  
...  
Keyword(s):  
Gap Junction ◽  
Genetic Basis ◽  
Behavioral Performance ◽  
Electrical Synapses ◽  
Network Function ◽  
Molecular Asymmetry ◽  
Metabolic Coupling ◽  
Neuronal Synapses ◽  
Chemical Synapses ◽  
And Function

AbstractNeural network function is based upon the patterns and types of connections made between neurons. Neuronal synapses are adhesions specialized for communication and they come in two types, chemical and electrical. Communication at chemical synapses occurs via neurotransmitter release whereas electrical synapses utilize gap junctions for direct ionic and metabolic coupling. Electrical synapses are often viewed as symmetrical structures, with the same components making both sides of the gap junction. By contrast, we show that a broad set of electrical synapses in zebrafish, Danio rerio, require two gap-junction-forming Connexins for formation and function. We find that one Connexin functions presynaptically while the other functions postsynaptically in forming the channels. We also show that these synapses are required for the speed and coordination of escape responses. Our data identify a genetic basis for molecular asymmetry at vertebrate electrical synapses and show they are required for appropriate behavioral performance.

scholarly journals Asymmetry of an intracellular scaffold at vertebrate electrical synapses

2017 ◽  
Author(s):  
Audrey J Marsh ◽  
Jennifer Carlisle Michel ◽  
Anisha P Adke ◽  
Emily L Heckman ◽  
Adam C Miller
Keyword(s):  
Gap Junction ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Electrical Synapse ◽  
Electrical Synapses ◽  
Gap Junction Channels ◽  
Junction Protein ◽  
Chemical Synapses ◽  
And Function

AbstractNeuronal synaptic connections are electrical or chemical and together are essential to dynamically defining neural circuit function. While chemical synapses are well known for their biochemical complexity, electrical synapses are often viewed as comprised solely of neuronal gap junction channels that allow direct ionic and metabolic communication. However, associated with the gap junction channels are structures observed by electron microscopy called the Electrical Synapse Density (ESD). The ESD has been suggested to be critical for the formation and function of the electrical synapse, yet the biochemical makeup of these structures is poorly understood. Here we find that electrical synapse formation in vivo requires an intracellular scaffold called Tight Junction Protein 1b (Tjp1b). Tjp1b is localized to electrical synapses where it is required for the stabilization of the gap junction channels and for electrical synapse function. Strikingly, we find that Tjp1b protein localizes and functions asymmetrically, exclusively on the postsynaptic side of the synapse. Our findings support a novel model in which there is molecular asymmetry at the level of the intracellular scaffold that is required for building the electrical synapse. ESD molecular asymmetries may be a fundamental motif of all nervous systems and could support functional asymmetry at the electrical synapse.

scholarly journals Author response: A genetic basis for molecular asymmetry at vertebrate electrical synapses

2017 ◽  
Author(s):  
Adam C Miller ◽  
Alex C Whitebirch ◽  
Arish N Shah ◽  
Kurt C Marsden ◽  
Michael Granato ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Author Response ◽  
Electrical Synapses ◽  
Molecular Asymmetry

Effects of Time Delay on Burst Synchronization Transition of Neuronal Networks

2018 ◽  
Vol 28 (12) ◽  
pp. 1850143 ◽  
Author(s):  
Xiaojuan Sun ◽  
Tianshu Xue
Keyword(s):  
Time Delay ◽  
Neuronal Network ◽  
Coupling Strength ◽  
Neuronal Networks ◽  
The Other ◽  
Electrical Synapses ◽  
Synchronization Transition ◽  
Burst Synchronization ◽  
Chemical Synapses ◽  
Bursting Activity

In this paper, we focus on investigating the effects of time delay on burst synchronization transitions of a neuronal network which is locally modeled by Hindmarsh–Rose neurons. Here, neurons inside the neuronal network are connected through electrical synapses or chemical synapses. With the numerical results, it is revealed that burst synchronization transitions of both electrically and chemically coupled neuronal networks could be induced by time delay just when the coupling strength is large enough. Meanwhile, it is found that, in electrically and excitatory chemically coupled neuronal networks, burst synchronization transitions are observed through change of spiking number per burst when coupling strength is large enough; while in inhibitory chemically coupled neuronal network, burst synchronization transitions are observed for large enough coupling strength through changing fold-Hopf bursting activity to fold-homoclinic bursting activity and vice versa. Namely, two types of burst synchronization transitions are observed. One type of burst synchronization transitions occurs through change of spiking numbers per burst and the other type of burst synchronization transition occurs through change of bursting types.

scholarly journals Electrical synaptic transmission requires a postsynaptic scaffolding protein

2020 ◽  
Author(s):  
Abagael M. Lasseigne ◽  
Fabio A. Echeverry ◽  
Sundas Ijaz ◽  
Jennifer Carlisle Michel ◽  
E. Anne Martin ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Gap Junctions ◽  
Functional Organization ◽  
Scaffolding Protein ◽  
Scaffolding Proteins ◽  
Electrical Transmission ◽  
Critical Function ◽  
Electrical Synapses ◽  
Intercellular Channels ◽  
Chemical Synapses

SUMMARYElectrical synaptic transmission relies on neuronal gap junctions containing channels constructed by Connexins. While at chemical synapses neurotransmitter-gated ion channels are critically supported by scaffolding proteins, it is unknown if channels at electrical synapses require similar scaffold support. Here we investigated the functional relationship between neuronal Connexins and Zonula Occludens 1 (ZO1), an intracellular scaffolding protein localized to electrical synapses. Using model electrical synapses in zebrafish Mauthner cells, we demonstrated that ZO1 is required for robust synaptic Connexin localization, but Connexins are dispensable for ZO1 localization. Disrupting this hierarchical ZO1/Connexin relationship abolishes electrical transmission and disrupts Mauthner-cell-initiated escape responses. We found that ZO1 is asymmetrically localized exclusively postsynaptically at neuronal contacts where it functions to assemble intercellular channels. Thus, forming functional neuronal gap junctions requires a postsynaptic scaffolding protein. The critical function of a scaffolding molecule reveals an unanticipated complexity of molecular and functional organization at electrical synapses.

scholarly journals Anisotropic Cardiac Conduction

2020 ◽  
Vol 9 (4) ◽  
pp. 202-210
Author(s):  
Irum Kotadia ◽  
John Whitaker ◽  
Caroline Roney ◽  
Steven Niederer ◽  
Mark O’Neill ◽  
...  
Keyword(s):  
Gap Junction ◽  
Cardiac Tissue ◽  
Diffusion Tensor ◽  
Interstitial Fibrosis ◽  
Cardiac Conduction ◽  
Principal Mechanism ◽  
Disease States ◽  
And Function ◽  
Anisotropic Conduction

Anisotropy is the property of directional dependence. In cardiac tissue, conduction velocity is anisotropic and its orientation is determined by myocyte direction. Cell shape and size, excitability, myocardial fibrosis, gap junction distribution and function are all considered to contribute to anisotropic conduction. In disease states, anisotropic conduction may be enhanced, and is implicated, in the genesis of pathological arrhythmias. The principal mechanism responsible for enhanced anisotropy in disease remains uncertain. Possible contributors include changes in cellular excitability, changes in gap junction distribution or function and cellular uncoupling through interstitial fibrosis. It has recently been demonstrated that myocyte orientation may be identified using diffusion tensor magnetic resonance imaging in explanted hearts, and multisite pacing protocols have been proposed to estimate myocyte orientation and anisotropic conduction in vivo. These tools have the potential to contribute to the understanding of the role of myocyte disarray and anisotropic conduction in arrhythmic states.

scholarly journals GJA1 Depletion Causes Ciliary Defects by Affecting Rab11 Trafficking to the Ciliary Base

2020 ◽  
Author(s):  
Dong Gil Jang ◽  
Keun Yeong Kwon ◽  
Yeong Cheon Kweon ◽  
Byung-gyu Kim ◽  
Kyungjae Myung ◽  
...  
Keyword(s):  
Gap Junction ◽  
Primary Cilium ◽  
Transport Channel ◽  
Junction Protein ◽  
Complex Functions ◽  
Mother Centriole ◽  
Pericentriolar Material ◽  
Gap Junction Protein ◽  
And Function ◽  
Distinct Distribution

AbstractThe gap junction complex functions as a transport channel across the membrane. Among gap junction subunits, gap junction protein alpha 1 (GJA1) is the most commonly expressed subunit. However, the roles of GJA1 in the formation and function of cilia remain unknown. Here, we examined GJA1 functions during ciliogenesis in vertebrates. GJA1 was localized to the motile ciliary axonemes or pericentriolar material (PCM) around the primary cilium. GJA1 depletion caused the severe malformation of both primary cilium and motile cilia. Interestingly, GJA1 depletion caused strong delocalization of BBS4 from the PCM and basal body and distinct distribution as cytosolic puncta. Further, CP110 removal from the mother centriole was significantly reduced by GJA1 depletion. Importantly, Rab11, key regulator during ciliogenesis, was immunoprecipitated with GJA1 and GJA1 knockdown caused the mis-localization and mis-accumulation of Rab11. These findings suggest that GJA1 is necessary for proper ciliogenesis by regulating the Rab11 pathway.

scholarly journals Regulation of Connexin Degradation as a Mechanism to Increase Gap Junction Assembly and Function

2000 ◽  
Vol 275 (33) ◽  
pp. 25207-25215 ◽  
Author(s):  
Linda S. Musil ◽  
Anh-Chi N. Le ◽  
Judy K. VanSlyke ◽  
Lori M. Roberts
Keyword(s):  
Gap Junction ◽  
And Function

scholarly journals Cardiomyopathy Classification: Ongoing Debate in the Genomics Era

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Charles McCartan ◽  
Robert Mason ◽  
S. R. Jayasinghe ◽  
Lyn R. Griffiths
Keyword(s):  
Adverse Effects ◽  
Genetic Information ◽  
Molecular Basis ◽  
Genetic Basis ◽  
Muscle Size ◽  
Systemic Diseases ◽  
Ongoing Debate ◽  
Traditional Classification ◽  
And Function

Cardiomyopathies represent a group of diseases of the myocardium of the heart and include diseases both primarily of the cardiac muscle and systemic diseases leading to adverse effects on the heart muscle size, shape, and function. Traditionally cardiomyopathies were defined according to phenotypical appearance. Now, as our understanding of the pathophysiology of the different entities classified under each of the different phenotypes improves and our knowledge of the molecular and genetic basis for these entities progresses, the traditional classifications seem oversimplistic and do not reflect current understanding of this myriad of diseases and disease processes. Although our knowledge of the exact basis of many of the disease processes of cardiomyopathies is still in its infancy, it is important to have a classification system that has the ability to incorporate the coming tide of molecular and genetic information. This paper discusses how the traditional classification of cardiomyopathies based on morphology has evolved due to rapid advances in our understanding of the genetic and molecular basis for many of these clinical entities.

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