Strength Of Electrical Synapses Research Articles

Effects of Propofol on Electrical Synaptic Strength in Coupling Reticular Thalamic GABAergic Parvalbumin-Expressing Neurons.

Electrical synapses between neurons exhibit a high degree of plasticity, which makes critical contributions to neuronal communication. The GABAergic parvalbumin-expressing (PV+) neurons in the thalamic reticular nucleus (TRN) interact with each other through electrical and chemical synapses. Plasticity of electrical synaptic transmission in TRN plays a key role in regulating thalamocortical and corticothalamic circuits and even the formation of consciousness. We here examined the effects of propofol, a commonly used general anesthetic agent, on the strength of electrical synapses between TRN PV+ neurons by fluorescence-guided patch-clamp recording and pharmacological methods. Results show that 100 μM propofol reduced the electrical synaptic strength between TRN PV+ neurons. Notably, the propofol-induced depression of electrical synaptic strength between TRN PV+ neurons was diminished by saclofen (10 μM, antagonist of GABAB receptors), but not blocked by gabazine (10 μM, antagonist of GABAA receptors). Application of baclofen (10 μM, agonist of GABAB receptors), similar to propofol, also reduced the electrical synaptic strength between TRN PV+ neurons. Moreover, the propofol-induced depression of electrical synaptic strength between TRN PV+ neurons was abolished by 9-CPA (100 μM, specific adenylyl cyclase inhibitor), and by KT5720 (1 μM, selective inhibitor of PKA). Our findings indicate that propofol acts on metabotropic GABAB receptors, resulting in a depression of electrical synaptic transmission of coupled TRN PV+ neurons, which is mediated by the adenylyl cyclase-cAMP-PKA signaling pathway. Our findings also imply that propofol may change the thalamocortical communication via inducing depression of electrical synaptic strength in the TRN.

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

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.

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

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.

A calcium-dependent pathway underlies activity-dependent plasticity of electrical synapses in the thalamic reticular nucleus.

Electrical synapses are modified by various forms of activity, including paired activity in coupled neurons and tetanization of the input to coupled neurons. We show that plasticity of electrical synapses that results from paired spiking activity in coupled neurons depends on calcium influx and calcium-initiated signalling pathways. Plasticity that results from tetanization of input fibres does not depend on calcium influx or dynamics. These results imply that electrically coupled neurons have distinct sets of mechanisms for adjusting coupling according to the specific type of activity they experience. Recent results have demonstrated modification of electrical synapse strength by varied forms of neuronal activity. However, the mechanisms underlying plasticity induction in central mammalian neurons are unclear. Here we show that the two established inductors of plasticity at electrical synapses in the thalamic reticular nucleus - paired burst spiking in coupled neurons, and mGluR-dependent tetanization of synaptic input - are separate pathways that converge at a common downstream endpoint. Using occlusion experiments and pharmacology in patched pairs of coupled neurons in vitro, we show that burst-induced depression depends on calcium entry via voltage-gated channels, is blocked by BAPTA chelation, and recruits intracellular calcium release on its way to activation of phosphatase activity. In contrast, mGluR-dependent plasticity is independent of calcium entry or calcium dynamics. Together, these results show that the spiking-initiated mechanisms underlying electrical synapse plasticity are similar to those that induce plasticity at chemical synapses, and offer the possibility that calcium-regulated mechanisms may also lead to alternate outcomes, such as potentiation. Because these mechanistic elements are widely found in mature neurons, we expect them to apply broadly to electrical synapses across the brain, acting as the crucial link between neuronal activity and electrical synapse strength.

A new measure for the strength of electrical synapses.

Electrical synapses, like chemical synapses, mediate intraneuronal communication. Electrical synapses are typically quantified by subthreshold measurements of coupling, which fall short in describing their impact on spiking activity in coupled neighbors. Here, we describe a novel measurement for electrical synapse strength that directly evaluates the effect of synaptically transmitted activity on spike timing. This method, also applicable to neurotransmitter-based synapses, communicates the considerable strength of electrical synapses. For electrical synapses measured in rodent slices of the thalamic reticular nucleus and in simple model neurons, spike timing is modulated by tens of ms by activity in a coupled neighbor.

Delay-induced synchronization transitions in modular scale-free neuronal networks with hybrid electrical and chemical synapses

We study the dependence of synchronization transitions in modular networks of bursting neurons with hybrid electrical–chemical synapses on the information transmission delay and the probability of electrical synapses. The modular network is composed of subnetworks (clusters); each of them presents the scale-free property. It is shown that, irrespective of the probability of electrical synapses, the time delay can always induce synchronization transitions in modular neuronal networks. Regions of synchronization and non-synchronization appear intermittently as the delay increases. In particular, all these transitions to burst synchronization occur approximately at integer multiples of oscillatory period of individual neurons. In addition, for larger probability of electrical synapses, the intermittent synchronization transition is more profound, due to the stronger synchronization capability of electrical synapses compared with chemical ones. Furthermore, the transition to synchronous bursting can also be induced by the variation of modular network parameters, that is, the coupling strength between neurons, the interconnection probability between different subnetworks, as well as the number of subnetworks. Particularly, we find that a modular neuronal network is harder to get global synchronization when constituting neurons are dispersed over more clusters. On the other hand, chemical and electrical synapses can perform complementary roles in the synchronization of hybrid modular neuronal networks: the larger the electrical synapse strength is the smaller the chemical synapse strength needed to achieve burst synchronization.

Delay-induced synchronization transitions in small-world neuronal networks with hybrid electrical and chemical synapses

We study the dependence of synchronization transitions in small-world networks of bursting neurons with hybrid electrical–chemical synapses on the information transmission delay, the probability of electrical synapses, and the rewiring probability. It is shown that, irrespective of the probability of electrical synapses, the information transmission delay can always induce synchronization transitions in small-world neuronal networks, i.e., regions of synchronization and nonsynchronization appear intermittently as the delay increases. In particular, all these transitions to burst synchronization occur approximately at integer multiples of the bursting period of individual neurons. In addition, for larger probability of electrical synapses, the intermittent synchronization transition is more profound, due to the stronger synchronization ability of electrical synapses compared with chemical ones. More importantly, chemical and electrical synapses can perform complementary roles in the synchronization of hybrid small-world neuronal networks: the larger the electrical synapse strength is, the smaller the chemical synapse strength needed to achieve burst synchronization. Furthermore, the small-world topology has a significant effect on the synchronization transition in hybrid neuronal networks. It is found that increasing the rewiring probability can always enhance the synchronization of neuronal activity. The results obtained are instructive for understanding the synchronous behavior of neural systems.

Bursts modify electrical synaptic strength

Changes in synaptic strength resulting from neuronal activity have been described in great detail for chemical synapses, but the relationship between natural forms of activity and the strength of electrical synapses had previously not been investigated. The thalamic reticular nucleus (TRN), a brain area rich in gap junctional (electrical) synapses, regulates cortical attention, initiates sleep spindles, and participates in shifts between states of arousal. Plasticity of electrical synapses in the TRN may be a key mechanism underlying these processes. Recently, we demonstrated a novel activity-dependent form of long-term depression of electrical synapses in the TRN (Haas et al., 2011). Here we provide an overview of those findings and discuss them in broader context. Because gap junctional proteins are widely expressed in the mammalian brain, modification of synaptic strength is likely to be a widespread and powerful mechanism at electrical synapses throughout the brain.

Trafficking of gap junction channels at a vertebrate electrical synapse in vivo

Trafficking and turnover of transmitter receptors required to maintain and modify the strength of chemical synapses have been characterized extensively. In contrast, little is known regarding trafficking of gap junction components at electrical synapses. By combining ultrastructural and in vivo physiological analysis at identified mixed (electrical and chemical) synapses on the goldfish Mauthner cell, we show here that gap junction hemichannels are added at the edges of GJ plaques where they dock with hemichannels in the apposed membrane to form cell-cell channels and, simultaneously, that intact junctional regions are removed from centers of these plaques into either presynaptic axon or postsynaptic dendrite. Moreover, electrical coupling is readily modified by intradendritic application of peptides that interfere with endocytosis or exocytosis, suggesting that the strength of electrical synapses at these terminals is sustained, at least in part, by fast (in minutes) turnover of gap junction channels. A peptide corresponding to a region of the carboxy terminus that is conserved in Cx36 and its two teleost homologs appears to interfere with formation of new gap junction channels, presumably by reducing insertion of hemichannels on the dendritic side. Thus, our data indicate that electrical synapses are dynamic structures and that their channels are turned over actively, suggesting that regulated trafficking of connexons may contribute to the modification of gap junctional conductance.

The Strength of Electrical Synapses

The strength of electrical synapses in the mammalian brain can be modulated by neuronal activity.

Combined effect of chemical and electrical synapses in Hindmarsh-Rose neural networks on synchronization and the rate of information

In this work we studied the combined action of chemical and electrical synapses in small networks of Hindmarsh-Rose (HR) neurons on the synchronous behavior and on the rate of information produced (per time unit) by the networks. We show that if the chemical synapse is excitatory, the larger the chemical synapse strength used the smaller the electrical synapse strength needed to achieve complete synchronization, and for moderate synaptic strengths one should expect to find desynchronous behavior. Otherwise, if the chemical synapse is inhibitory, the larger the chemical synapse strength used the larger the electrical synapse strength needed to achieve complete synchronization, and for moderate synaptic strengths one should expect to find synchronous behaviors. Finally, we show how to calculate semianalytically an upper bound for the rate of information produced per time unit (Kolmogorov-Sinai entropy) in larger networks. As an application, we show that this upper bound is linearly proportional to the number of neurons in a network whose neurons are highly connected.

Long-Term Modulation of Electrical Synapses in the Mammalian Thalamus

Electrical synapses are common between inhibitory neurons in the mammalian thalamus and neocortex. Synaptic modulation, which allows flexibility of communication between neurons, has been studied extensively at chemical synapses, but modulation of electrical synapses in the mammalian brain has barely been examined. We found that the activation of metabotropic glutamate receptors, via endogenous neurotransmitter or by agonist, causes long-term reduction of electrical synapse strength between the inhibitory neurons of the rat thalamic reticular nucleus.

Intrinsic modulation of pulse-coupled integrate-and-fire neurons

Intrinsic neuromodulation is observed in sensory and neuromuscular circuits and in biological central pattern generators. We model a simple neuronal circuit with a system of two pulse-coupled integrate-and-fire neurons and explore the parameter regimes for periodic firing behavior. The inclusion of biologically realistic features shows that the speed and onset of neuronal response plays a crucial role in determining the firing phase for periodic rhythms. We explore the neurophysiological function of distributed delays arising from both the synaptic transmission process and dendritic structure as well as discrete delays associated with axonal communication delays. Bifurcation and stability diagrams are constructed with a mixture of simple analysis, numerical continuation and the Kuramoto phase-reduction technique. Moreover, we show that, for asynchronous behavior, the strength of electrical synapses can control the firing rate of the system.