The effector and scaffolding proteins AF6 and MUPP1 interact with connexin36 and localize at gap junctions that form electrical synapses in rodent brain

2011 ◽  
Vol 35 (2) ◽  
pp. 166-181 ◽  
Author(s):  
X. Li ◽  
B. D. Lynn ◽  
J. I. Nagy
2020 ◽  
Author(s):  
Abagael M. Lasseigne ◽  
Fabio A. Echeverry ◽  
Sundas Ijaz ◽  
Jennifer Carlisle Michel ◽  
E. Anne Martin ◽  
...  

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.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Abagael M Lasseigne ◽  
Fabio A Echeverry ◽  
Sundas Ijaz ◽  
Jennifer Carlisle Michel ◽  
E Anne Martin ◽  
...  

Electrical 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.


2019 ◽  
Author(s):  
Gordon B. Feld ◽  
Hong-Viet Ngo ◽  
Ernesto Durán ◽  
Sandra Gebhardt ◽  
Lisa Kleist ◽  
...  

AbstractDuring sleep, the time-compressed replay of engrams acquired during preceding wakefulness drives memory consolidation. We demonstrate in healthy humans that direct electrical coupling between neurons via gap junctions, i.e., electrical synapses, contributes to this beneficial effect of sleep. Twenty male participants learned a declarative word-pair task and a procedural finger sequence tapping task before receiving the antimalarial mefloquine that is known to block electrical synapses. Retrieval was tested after a retention interval of approximately 20.5 hours that included nocturnal sleep. As predicted, mefloquine given before sleep impaired the retention of declarative memory. In contrast, this effect was absent in control groups, which stayed awake or received mefloquine after sleep. Irrespective of sleep or administration time, mefloquine enhanced retention performance on the procedural memory control task. We conclude that sleep-dependent processes relying on electrical neuronal coupling enable hippocampus-dependent declarative memory consolidation, presumably via time-compressed hippocampal replay of memory traces within sharp-wave/ripple complexes. The recruitment of this understudied form of neuronal information transfer may be necessary to achieve fast-paced memory reprocessing during sleep. Considering that drugs targeting neurochemical synapses have recently fallen short of substantially advancing the treatment of memory impairments in Alzheimer’s disease, schizophrenia or during normal aging, unraveling the contribution of gap junctions to sleep-dependent declarative memory formation can be expected to open new therapeutic avenues.Significance statementSleep supports the strengthening and transformation of memory content via the active replay of previously encoded engrams. Surprisingly, blocking neurochemical synaptic transmission does not impair this function of sleep. Here we demonstrate that the direct electrical coupling between neurons via electrical synapses (gap junctions) is essential for the sleep-dependent formation of declarative memory, i.e., memory for episodes and facts. These findings are in line with the assumption that electrical synapses enable time-compressed neuronal firing patterns that emerge during sleep and drive declarative memory consolidation. Electrical synapses have so far not been linked to higher-order brain functions in humans; their contribution to sleep-dependent memory processing may provide a novel target for sleep-related clinical interventions.


2017 ◽  
Vol 114 (46) ◽  
pp. E9962-E9971 ◽  
Author(s):  
Sudeshna Das ◽  
Federica Trona ◽  
Mohammed A. Khallaf ◽  
Elisa Schuh ◽  
Markus Knaden ◽  
...  

In Drosophila melanogaster, the sex pheromone produced by males, cis-vaccenyl acetate (cVA), evokes a stereotypic gender-specific behavior in both males and females. As Drosophila adults feed, mate, and oviposit on food, they perceive the pheromone as a blend against a background of food odors. Previous studies have reported that food odors enhance flies’ behavioral response to cVA, specifically in virgin females. However, how and where the different olfactory inputs interact has so far remained unknown. In this study, we elucidated the neuronal mechanism underlying the response at an anatomical, functional, and behavioral level. Our data show that in virgin females cVA and the complex food odor vinegar evoke a synergistic response in the cVA-responsive glomerulus DA1. This synergism, however, does not appear at the input level of the glomerulus, but is restricted to the projection neuron level only. Notably, it is abolished by a mutation in gap junctions in projection neurons and is found to be mediated by electrical synapses between excitatory local interneurons and projection neurons. As a behavioral consequence, we demonstrate that virgin females in the presence of vinegar become receptive more rapidly to courting males, while male courtship is not affected. Altogether, our results suggest that lateral excitation via gap junctions modulates odor tuning in the antennal lobe and drives synergistic interactions between two ecologically relevant odors, representing food and sex.


2014 ◽  
Vol 112 (9) ◽  
pp. 2102-2113 ◽  
Author(s):  
Cong Yao ◽  
Kimberly G. Vanderpool ◽  
Matthew Delfiner ◽  
Vanessa Eddy ◽  
Alexander G. Lucaci ◽  
...  

In contrast to the knowledge of chemical synapses, little is known regarding the properties of gap junction-mediated electrical synapses in developing zebrafish, which provide a valuable model to study neural function at the systems level. Identifiable “mixed” (electrical and chemical) auditory synaptic contacts known as “club endings” on Mauthner cells (2 large reticulospinal neurons involved in tail-flip escape responses) allow exploration of electrical transmission in fish. Here, we show that paralleling the development of auditory responses, electrical synapses at these contacts become anatomically identifiable at day 3 postfertilization, reaching a number of ∼6 between days 4 and 9. Furthermore, each terminal contains ∼18 gap junctions, representing between 2,000 and 3,000 connexon channels formed by the teleost homologs of mammalian connexin 36. Electrophysiological recordings revealed that gap junctions at each of these contacts are functional and that synaptic transmission has properties that are comparable with those of adult fish. Thus a surprisingly small number of mixed synapses are responsible for the acquisition of auditory responses by the Mauthner cells, and these are likely sufficient to support escape behaviors at early developmental stages.


2021 ◽  
Vol 22 (9) ◽  
pp. 4473
Author(s):  
Georg R. Zoidl ◽  
David C. Spray

Anatomical and electrophysiological evidence that gap junctions and electrical coupling occur between neurons was initially confined to invertebrates and nonmammals and was thought to be a primitive form of synaptic transmission. More recent studies revealed that electrical communication is common in the mammalian central nervous system (CNS), often coexisting with chemical synaptic transmission. The subsequent progress indicated that electrical synapses formed by the gap junction protein connexin-36 (Cx36) and its paralogs in nonmammals constitute vital elements in mammalian and fish synaptic circuitry. They govern the collective activity of ensembles of coupled neurons, and Cx36 gap junctions endow them with enormous adaptive plasticity, like that seen at chemical synapses. Moreover, they orchestrate the synchronized neuronal network activity and rhythmic oscillations that underlie the fundamental integrative processes, such as memory and learning. Here, we review the available mechanistic evidence and models that argue for the essential roles of calcium, calmodulin, and the Ca2+/calmodulin-dependent protein kinase II in integrating calcium signals to modulate the strength of electrical synapses through interactions with the gap junction protein Cx36.


Author(s):  
Q. Bone ◽  
K. P. Ryan

The bristle-bearing receptors on either side of the trunk in Oikopleura are connected to the caudal ganglion by the axons of central cells which form electrical synapses (gap junctions) at the bases of the receptor cells. The same axons also form similar synapses with epithelial cells adjacent to the receptors. Direct mechanical stimulation of the receptor processes evokes changes in the locomotor rhythm of the same kind as evoked by action potentials propagated in the epithelial cells. This remarkable arrangement is suggested to be a consequence of the reduced numbers of cells in larvaceans.


Neuron ◽  
2016 ◽  
Vol 90 (2) ◽  
pp. 207-209 ◽  
Author(s):  
Jonathan B. Demb ◽  
Joshua H. Singer

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