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Electrical synapses and their functional interactions with chemical synapses

Key Points

  • There are two main modalities of synaptic transmission: chemical and electrical. Although chemical synapses are perceived to be structurally more complex and functionally dynamic than electrical synapses, emerging evidence indicates that electrical synapses might be similarly complex, functionally diverse and highly modifiable.

  • Far from functioning independently and serving unrelated functions, these two modalities of synaptic transmission closely interact. Rather than conceiving synaptic transmission as either chemical or electrical, this article emphasizes the notion that synaptic transmission is both chemical and electrical, and that interactions between these two forms of interneuronal communication are required for normal brain development and function.

  • The development of neural circuits in disparate nervous systems (both vertebrate and invertebrate) seems to rely critically on interactions between chemical and electrical synapses, which reciprocally and dynamically regulate the emergence of these two forms of transmission.

  • During development, interactions between electrical synapses are crucial for the formation of neural circuits; however, such interactions in the adult brain result in dynamic reconfiguration of hardwired networks. The strength of electrical synapses is regulated by neuromodulaters such as dopamine and by glutamatergic synapses in an activity-dependent manner.

  • Interactions between electrical and chemical synapses are also likely to have important pathological implications. Recapitulation of developmental interactions between chemical and electrical synapses has been observed after brain injury, and dysregulation of electrical synapses by neurotransmitters could contribute to cognitive impairment.

Abstract

Brain function relies on the ability of neurons to communicate with each other. Interneuronal communication primarily takes place at synapses, where information from one neuron is rapidly conveyed to a second neuron. There are two main modalities of synaptic transmission: chemical and electrical. Far from functioning independently and serving unrelated functions, mounting evidence indicates that these two modalities of synaptic transmission closely interact, both during development and in the adult brain. Rather than conceiving synaptic transmission as either chemical or electrical, this article emphasizes the notion that synaptic transmission is both chemical and electrical, and that interactions between these two forms of interneuronal communication might be required for normal brain development and function.

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Figure 1: The two main modalities of synaptic transmission.
Figure 2: Trafficking of channels at chemical and electrical synapses.
Figure 3: Electrical and chemical synapses interact during development.
Figure 4: Types of interactions between electrical and chemical synapses in the adult nervous system.
Figure 5: Interactions between electrical synapses and inhibitory chemical synapses.
Figure 6: Interactions between chemical and electrical synapses and pathological processes.

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Acknowledgements

This research was supported by US National Institutes of Health grants DC03186, DC011099, NS055726, NS085772 and NS0552827 to A.E.P.

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Glossary

Lateral excitation

The ability of an excited neuron (or sensory afferent) to excite its neighbours. Although it reduces discrimination, lateral excitation greatly enhances input sensitivity. It is a less-appreciated property of sensory and cortical networks.

Escape networks

Neural networks found in invertebrate and vertebrate nervous systems (usually containing a small number of cells that include sensory and motor neurons) that seem optimized to mediate fast escape behaviours.

Mauthner cell

A large reticulospinal neuron found in teleost fish that mediates (among other functions) tail-flip sensory-evoked escape responses.

Postsynaptic density

(PSD). Originally named after its identification by electron microscopy, the term refers to a macromolecular complex that supports postsynaptic function at chemical synapses and includes neurotransmitters receptors, scaffolding proteins and regulatory signalling molecules.

PSD95

(Postsynaptic density protein 95). A protein that contains multiple domains that mediate its association with receptors, cell-adhesion molecules and cytoplasmic signalling molecules. By virtue of these interactions, it influences the surface delivery, stability and subcellular location of postsynaptic receptors, and facilitates their functional coupling to downstream signalling pathways.

Electroretinography

An extracellularly recorded electrical response that reflects the activation of various cells in the retina (including photoreceptors, inner retinal cells and the output ganglion cells) in response to visual stimulation.

ON bipolar cells

Retinal cells that functionally link photoreceptors (cones and rods) to ganglion cells. ON bipolar cells are excited by the release of glutamate from photoreceptors, whereas OFF bipolar cells are instead inhibited.

All type amacrine cells

The AII is a type of amacrine cell (a class of retinal interneuron) that relays rod-driven information through the ON-centre cone bipolar axons to ON-centre ganglion cells (output neurons of the retina) via electrical synapses.

Associative binding

The term refers to tasks of episodic memory that require the associative combining of distinct components into a compound episode.

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Pereda, A. Electrical synapses and their functional interactions with chemical synapses. Nat Rev Neurosci 15, 250–263 (2014). https://doi.org/10.1038/nrn3708

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