On the Diverse Functions of Electrical Synapses

Abstract

Electrical synapses are the neurophysiological product of gap junctional pores between neurons that allow bidirectional flow of current between neurons. They are expressed throughout the mammalian nervous system, including cortex, hippocampus, thalamus, retina, cerebellum, and inferior olive. Classically, the function of electrical synapses has been associated with synchrony, logically following that continuous conductance provided by gap junctions facilitates the reduction of voltage differences between coupled neurons. Indeed, electrical synapses promote synchrony at many anatomical and frequency ranges across the brain. However, a growing body of literature shows there is greater complexity to the computational function of electrical synapses. The paired membranes that embed electrical synapses act as low-pass filters, and as such, electrical synapses can preferentially transfer spike after hyperpolarizations, effectively providing spike-dependent inhibition. Other functions include driving asynchronous firing, improving signal to noise ratio, aiding in discrimination of dissimilar inputs, or dampening signals by shunting current. The diverse ways by which electrical synapses contribute to neuronal integration merits furthers study. Here we review how functions of electrical synapses vary across circuits and brain regions and depend critically on the context of the neurons and brain circuits involved. Computational modeling of electrical synapses embedded in multi-cellular models and experiments utilizing optical control and measurement of cellular activity will be essential in determining the specific roles performed by electrical synapses in varying contexts.

Keywords: connexin; electrical synapse; gap junction; integration; synchrony.

FIGURE 1

Electrical synapses have diverse functions in neural processing. (A) Example of synchronous activity in coupled neurons (adapted from Long et al., 2004). (B) Example of anti-synchronous firing in coupled neurons (adapted from Vervaeke et al., 2010). (C) An electrical synapse (right) shunts an excitatory signal to one cell to subthreshold levels, compared to the uncoupled case (left) (adapted from Hjorth et al., 2009). (D) Slow spike afterhyperpolarizations appear as inhibition in a coupled neuron (adapted from Galarreta and Hestrin, 2001). (E) Spikes result in excitation in a coupled neuron (adapted from Apostolides and Trussell, 2014). (F) Example of a signal amidst noise in retinal neurons, impacted by the presence of electrical synapses (adapted from Dunn et al., 2006).