Electrical synapses regulate both subthreshold integration and population activity of principal cells in response to transient inputs within canonical feedforward circuits

Abstract

As 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 exert either excitatory or inhibitory pulses of influence on the postsynaptic neuron, electrical synapses, composed of plaques of gap junction channels, continuously transmit signals 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 synapse strength on both 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.

Activity-dependent long-term potentiation of electrical synapses in the mammalian thalamus

“…Further, these numerically modest changes in synaptic strength yield 5-10 ms changes in 154 spike times in coupled neighbors (Haas, 2015). Computational models reinforce the 155 effectiveness of changes in coupling in this range (Pham & Haas, 2018, 2019. Thus, even 156 seemingly modest changes in electrical synapse strength produce physiologically substantial 157 effects, and are poised to exert major influence on TRN synchrony and processing.…”

“…In the mature mammalian brain, electrical synapses are composed of paired hexomers 37 of connexin36 that pass ions and small molecules, and mainly couple inhibitory GABAergic 38 neurons (Bennett & Zukin, 2004;Connors & Long, 2004;Galarreta & Hestrin, 2001). Electrical 39 synapses contribute to synchrony in coupled networks (Chow & Kopell, 2000;Destexhe, 1998; Whittington & Traub, 2003) and regulate timing of 42 spikes in the neurons they couple (Haas, 2015;Pham & Haas, 2018, 2019. Despite their 43 prevalence and function between spiking neurons across the brain, the effects of neuronal 44 activity on connection strength remain sparsely characterized.…”

Electrical synapse asymmetry results from, and masks, neuronal heterogeneity

“…To address the impact of neuronal excitability and morphology on electrical synapse communication, we built a three-compartment TRN cell model based on those previously used (McCormick & Huguenard, 1992;Pham & Haas, 2018, 2019Traub et al, 2005). To validate the model's dendritic geometry, we used coupling between compartments that generated reasonable amplitudes of backpropagated single spikes (Figure 1A), and sublinear dendritic responses to AMPAergic current injections (Figure 1B) (Connelly et al, 2017).…”

“…In a model thalamocortical circuit, coupling amongst feedback inhibitory neurons enhances discrimination of inputs sent to cortex by relay cells (Pham & Haas, 2018). In a canonical model circuit with feedforward inhibition, electrical synapses enhance subthreshold integration (Pham & Haas, 2019). In a toadfish vocal circuit, electrical coupling between feedforward inhibitory neurons enhances synchrony and temporal precision (Chagnaud et al, 2021) and a similar effect occurs for cerebellar basket cells (Hoehne et al, 2020).…”

Feed-forward recruitment of electrical synapses enhances synchronous spiking in the mouse cerebellar cortex

“…Finally, the presence of electrical synapses has been shown to modulate passive properties in interneurons ( Alcami, 2018 ; Amsalem et al, 2016 ; Hjorth et al, 2009 ). However, despite theoretical studies showing the influence of electrical synapses in information processing within FF circuits ( Pham and Haas, 2019 ), experimental evidence that electrical synapses modify temporally coded information within FF neural circuits has not been demonstrated.…”