The Role of Intrinsic Cell Properties in Synchrony of Neurons Interacting via Electrical Synapses

Tubulin-Dependent Transport of Connexin-36 Potentiates the Size and Strength of Electrical Synapses

Cells ◽

10.3390/cells8101146 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1146 ◽

Cited By ~ 4

Author(s):

Brown ◽

del Corsso ◽

Zoidl ◽

Donaldson ◽

Spray ◽

...

Keyword(s):

Protein Transport ◽

Mutational Analysis ◽

Binding Motif ◽

Dependent Manner ◽

Electrical Synapses ◽

Binding Motifs ◽

Connexin 36 ◽

Dependent Transport ◽

Carboxy Terminal

Connexin-36 (Cx36) electrical synapses strengthen transmission in a calcium/calmodulin (CaM)/calmodulin-dependent kinase II (CaMKII)-dependent manner similar to a mechanism whereby the N-methyl-D-aspartate (NMDA) receptor subunit NR2B facilitates chemical transmission. Since NR2B–microtubule interactions recruit receptors to the cell membrane during plasticity, we hypothesized an analogous modality for Cx36. We determined that Cx36 binding to tubulin at the carboxy-terminal domain was distinct from Cx43 and NR2B by binding a motif overlapping with the CaM and CaMKII binding motifs. Dual patch-clamp recordings demonstrated that pharmacological interference of the cytoskeleton and deleting the binding motif at the Cx36 carboxyl-terminal (CT) reversibly abolished Cx36 plasticity. Mechanistic details of trafficking to the gap-junction plaque (GJP) were probed pharmacologically and through mutational analysis, all of which affected GJP size and formation between cell pairs. Lys279, Ile280, and Lys281 positions were particularly critical. This study demonstrates that tubulin-dependent transport of Cx36 potentiates synaptic strength by delivering channels to GJPs, reinforcing the role of protein transport at chemical and electrical synapses to fine-tune communication between neurons.

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Exact Mean-Field Theory Explains the Dual Role of Electrical Synapses in Collective Synchronization

Physical Review Letters ◽

10.1103/physrevlett.125.248101 ◽

2020 ◽

Vol 125 (24) ◽

Author(s):

Ernest Montbrió ◽

Diego Pazó

Keyword(s):

Field Theory ◽

Mean Field Theory ◽

Mean Field ◽

Dual Role ◽

Electrical Synapses

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Function and Plasticity of Electrical Synapses in the Mammalian Brain: Role of Non-Junctional Mechanisms

10.20944/preprints202112.0384.v1 ◽

2021 ◽

Author(s):

Sebastian Curti ◽

Federico Davoine ◽

Antonella Dapino

Keyword(s):

Molecular Mechanisms ◽

Mammalian Brain ◽

Synaptic Membrane ◽

Electrical Transmission ◽

Electrical Synapses ◽

Electrophysiological Properties ◽

Voltage Dependent ◽

Theoretical Evidence ◽

Circuit Function

Electrical transmission between neurons is largely mediated by gap junctions. These junctions allow the direct flow of electric current between neurons, and in mammals are mostly composed of the protein connexin (Cx)36. Circuits of electrically coupled neurons are widespread in these animals, plus, experimental and theoretical evidence supports the notion that, beyond synchronicity, these circuits are able to perform sophisticated operations like lateral excitation and inhibition, noise reduction, as well as the ability to selectively respond upon coincident excitatory inputs. Although once considered stereotyped and unmodifiable, we now know that electrical synapses are subject to modulation and, by reconfiguring neural circuits, these modulations can alter relevant operations. The strength of electrical synapses depends on gap junction conductance, as well as on its functional interaction with the electrophysiological properties of coupled neurons. In particular, voltage dependent channels of the non-synaptic membrane critically determine the efficacy of transmission at these contacts. Consistently, modulatory actions on these channels have been shown to represent relevant mechanisms of plasticity of electrical synaptic transmission. Here we review recent evidence on the regulation of electrical synapses of mammals, the underlying molecular mechanisms, and the possible ways in which they affect circuit function.

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Electrical Synapses and Synchrony: The Role of Intrinsic Currents

Journal of Neuroscience ◽

10.1523/jneurosci.23-15-06280.2003 ◽

2003 ◽

Vol 23 (15) ◽

pp. 6280-6294 ◽

Cited By ~ 122

Author(s):

Benjamin Pfeuty ◽

Germán Mato ◽

David Golomb ◽

David Hansel

Keyword(s):

Electrical Synapses

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Attenuation of Neuropathic Pain by Inhibiting Electrical Synapses in the Anterior Cingulate Cortex

Anesthesiology ◽

10.1097/aln.0000000000000942 ◽

2016 ◽

Vol 124 (1) ◽

pp. 169-183 ◽

Cited By ~ 13

Author(s):

Zhi-Yu Chen ◽

Feng-Yan Shen ◽

Lai Jiang ◽

Xuan Zhao ◽

Xiao-Lu Shen ◽

...

Keyword(s):

Neuropathic Pain ◽

Synaptic Plasticity ◽

Anterior Cingulate Cortex ◽

Nerve Injury ◽

Cingulate Cortex ◽

Gamma Oscillations ◽

Anterior Cingulate ◽

Neuronal Oscillations ◽

Electrical Synapses

Abstract Background Synaptic mechanisms and neuronal oscillations have been proposed to be responsible for neuropathic pain formation. Many studies have also highlighted the important role of electrical synapses in synaptic plasticity and in neuronal oscillations. Thus, electrical synapses may contribute to neuropathic pain generation. However, previous studies have primarily focused on the role of chemical synapses, while ignoring the role of electrical synapses, in neuropathic pain generation. Methods The authors adopted microinjection, RNA interference techniques, and behavioral tests to verify the link between connexin 36 (Cx36) and neuropathic pain. They also studied the selective Cx36 blocker mefloquine in rat chronic constriction injury and spared nerve injury model of neuropathic pain. Electrophysiologic recordings were used to further confirm the behavioral data. Results The authors found that Cx36, which constitutes the neuron–neuron electrical synapses, was up-regulated in the anterior cingulate cortex after nerve injury (n = 5). Meanwhile, Cx36-mediated neuronal oscillations in the gamma frequency range (30 to 80 Hz) (n = 7 to 8) and the neuronal synaptic transmission (n = 13 to 19) were also enhanced. Neuropathic pain was relieved by disrupting Cx36 function or expression in the anterior cingulate cortex. They also found that mefloquine, which are clinically used for treating malaria, affected gamma oscillations and synaptic plasticity, leading to a sustained pain relief in chronic constriction injury and spared nerve injury models (n = 7 to 12). Conclusion The electrical synapses blocker mefloquine could affect gamma oscillations and synaptic plasticity in the anterior cingulate cortex and relieve neuropathic pain. Cx36 may be a new therapeutic target for treating chronic pain.

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Electrical synapses and transient signals in feedforward canonical circuits

10.1101/394593 ◽

2018 ◽

Author(s):

Tuan Pham ◽

Julie S. Haas

Keyword(s):

Signal Processing ◽

Computational Models ◽

Transient Signal ◽

Electrical Synapses ◽

Transient Signals ◽

Network Information ◽

Growing Body ◽

Neuronal Processing ◽

The Brain

AbstractAs information about the world traverses the brain, the signals exchanged between neurons are passed and modulated by synapses, or specialized contacts between neurons. While neurotransmitter-based synapses tend to be either relay excitatory or inhibitory pulses of influence on the postsynaptic neuron, electrical synapses, composed of plaques of gap junction channels, are always-on transmitters that can either excite or inhibit a coupled neighbor. A growing body of evidence indicates that electrical synapses, similar to their chemical counterparts, are modified in strength during physiological neuronal activity. The synchronizing role of electrical synapses in neuronal oscillations has been well established, but their impact on transient signal processing in the brain is much less understood. Here we constructed computational models based on the canonical feedforward neuronal circuit, and included electrical synapses between inhibitory interneurons. We provided discrete closely-timed inputs to the circuits, and characterize the influence of electrical synapses on both the subthreshold summation and spike trains in the output neuron. Our simulations highlight the diverse and powerful roles that electrical synapses play even in simple circuits. Because these canonical circuits are represented widely throughout the brain, we expect that these are general principles for the influence of electrical synapses on transient signal processing across the brain.Author SummaryThe role that electrical synapses play in neural oscillations, network synchronization and rhythmicity is well established, but their role neuronal processing of transient inputs is much less understood. Here we used computational models of canonical feedforward circuits and networks to investigate how the strength of electrical synapses regulates the flow of transient signals passing through those circuits. We show that because the influence of electrical synapses on coupled neighbors can be either inhibitory or excitatory, their role in network information processing is heterogeneous.. Because of the widespread existence of electrical synapses between interneurons as well as a growing body of evidence for their plasticity, we expect such effects play a significant role in how the brain processes transient inputs.

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Physical model of electrical synapses in a neural network

10.1101/2021.12.13.472453 ◽

2021 ◽

Author(s):

Mikhail Pekker ◽

Mikhail Shneider

Keyword(s):

Neural Network ◽

Theoretical Model ◽

Action Potential ◽

Physical Model ◽

Nodes Of Ranvier ◽

Myelinated Axons ◽

Active Neuron ◽

Electrical Synapses ◽

Ephaptic Coupling

A theoretical model of electrical synapses is proposed, in which connexons play the role of nails that hold unmyelinated areas of neurons at a distance of about 3.5 nm, and the electrical connection between them is provided by charging the membrane of an inactive neuron with currents generated in the intercellular electrolyte (saline) by the action potential in the active neuron. This mechanism is similar to the salutatory conduction of the action potential between the nodes of Ranvier in myelinated axons and the ephaptic coupling of sufficiently close spaced neurons.

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Function and Plasticity of Electrical Synapses in the Mammalian Brain: Role of Non-Junctional Mechanisms

Biology ◽

10.3390/biology11010081 ◽

2022 ◽

Vol 11 (1) ◽

pp. 81

Author(s):

Sebastian Curti ◽

Federico Davoine ◽

Antonella Dapino

Keyword(s):

Molecular Mechanisms ◽

Mammalian Brain ◽

Synaptic Membrane ◽

Electrical Transmission ◽

Electrical Synapses ◽

Electrophysiological Properties ◽

Theoretical Evidence ◽

Circuit Function ◽

Lateral Excitation

Electrical transmission between neurons is largely mediated by gap junctions. These junctions allow the direct flow of electric current between neurons, and in mammals, they are mostly composed of the protein connexin36. Circuits of electrically coupled neurons are widespread in these animals. Plus, experimental and theoretical evidence supports the notion that, beyond synchronicity, these circuits are able to perform sophisticated operations such as lateral excitation and inhibition, noise reduction, as well as the ability to selectively respond upon coincident excitatory inputs. Although once considered stereotyped and unmodifiable, we now know that electrical synapses are subject to modulation and, by reconfiguring neural circuits, these modulations can alter relevant operations. The strength of electrical synapses depends on the gap junction resistance, as well as on its functional interaction with the electrophysiological properties of coupled neurons. In particular, voltage and ligand gated channels of the non-synaptic membrane critically determine the efficacy of transmission at these contacts. Consistently, modulatory actions on these channels have been shown to represent relevant mechanisms of plasticity of electrical synaptic transmission. Here, we review recent evidence on the regulation of electrical synapses of mammals, the underlying molecular mechanisms, and the possible ways in which they affect circuit function.

Download Full-text