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.
more »
« less
The dynamic range of voltage-dependent gap junction signaling is maintained by I h -induced membrane potential depolarization
Like their chemical counterparts, electrical synapses show complex dynamics such as rectification and voltage dependence that interact with other electrical processes in neurons. The consequences arising from these interactions for the electrical behavior of the synapse, and the dynamics they create, remain largely unexplored. Using a voltage-dependent electrical synapse between a descending modulatory projection neuron (MCN1) and a motor neuron (LG) in the crustacean stomatogastric ganglion, we find that the influence of the hyperpolarization-activated inward current ( I h ) is critical to the function of the electrical synapse. When we blocked I h with CsCl, the apparent voltage dependence of the electrical synapse shifted by 18.7 mV to more hyperpolarized voltages, placing the dynamic range of the electrical synapse outside of the range of voltages used by the LG motor neuron (−60.2 mV to −44.9 mV). With dual electrode current- and voltage-clamp recordings, we demonstrate that this voltage shift is not due to a change in the properties of the gap junction itself, but is a result of a sustained effect of I h on the presynaptic MCN1 axon terminal membrane potential. I h -induced depolarization of the axon terminal membrane potential increased the electrical postsynaptic potentials and currents. With I h present, the axon terminal resting membrane potential is depolarized, shifting the dynamic range of the electrical synapse toward the functional range of the motor neuron. We thus demonstrate that the function of an electrical synapse is critically influenced by a voltage-dependent ionic current ( I h ). NEW & NOTEWORTHY Electrical synapses and voltage-gated ionic currents are often studied independently from one another, despite mounting evidence that their interactions can alter synaptic behavior. We show that the hyperpolarization-activated inward ionic current shifts the voltage dependence of electrical synaptic transmission through its depolarizing effect on the membrane potential, enabling it to lie within the functional membrane potential range of a motor neuron. Thus, the electrical synapse’s function critically depends on the voltage-gated ionic current.
more »
« less
- PAR ID:
- 10340498
- Date Published:
- Journal Name:
- Journal of Neurophysiology
- Volume:
- 127
- Issue:
- 3
- ISSN:
- 0022-3077
- Page Range / eLocation ID:
- 776 to 790
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Neuromorphic computing is considered to have the potential to overcome the limitations of traditional von Neumann architecture due to its high efficiency, low energy consumption, and fault-tolerance. Hardware components that can emulate the synaptic plasticity of neurons, i.e. artificial synaptic devices, are required by neuromorphic systems. New devices have been examined for such components, such as phase-change artificial synapse, ferroelectric artificial synapse, and memristor synapses. Among them, memristor, a two-terminal metal-insulator-metal structure that are analogous to a biological synapse with presynaptic neuron (top electrode), postsynapticneuron (bottom electrode), and synaptic cleft (memristive film), is a promising device technology because of its tunable resistance, scalability, 3D integration compatibility, low power consumption, and relatively high speed. In contrary to inorganic materials such as metal oxides, natural organic materials have attracted interest to form the memristive layer because they are renewable, biodegradable, sustainable, biocompatible, and environmentally friendly. In this paper, honey solution embedded with carbon nanotubes (CNTs) was processed into the memristive layer by a low cost solution-based process, with synaptic plasticity of the final honey-CNT memristors characterized, including forget and relearn, spike-rate-dependent plasticity, spike-voltage-dependent plasticity, short-term to long-term memory transition, paired pulse facilitation, and spatial supra-linear summation behaviors. The successful emulation of these essential biological synaptic behaviors demonstrates the potential of honey-CNT memristors as a viable hardware component in neuromorphic computing systems.more » « less
-
Synaptic plasticity, the dynamic tuning of signal transmission strength between neurons, serves as a fundamental basis for memory and learning in biological organisms. This adaptive nature of synapses is considered one of the key features contributing to the superior energy efficiency of the brain. Here, we use molecular dynamics simulations to demonstrate synaptic-like plasticity in a subnanoporous two-dimensional membrane. We show that a train of voltage spikes dynamically modifies the membrane’s ionic permeability in a process involving competitive bicationic transport. This process is shown to be repeatable after a given resting period. Because of a combination of subnanometer pore size and the atomic thinness of the membrane, this system exhibits energy dissipation of 0.1 to 100 aJ per voltage spike, which is several orders of magnitude lower than 0.1 to 10 fJ per spike in the human synapse. We reveal the underlying physical mechanisms at molecular detail and investigate the local energetics underlying this apparent synaptic-like behavior.more » « less
-
Retinal prosthetic systems have been developed to help blind patients suffering from retinal degenerative diseases gain some useful form of vision. Various experimental and computational studies have been performed to test electrical stimulation strategies that can improve the performance of these devices. Detailed computational models of retinal neurons, such as retinal ganglion cells (RGCs) and bipolar cells (BCs), allow us to explore the mechanisms underlying the response of cells to electrical stimulation. While electrophysiological studies have shown the presence of voltage-gated ionic channels in different regions of BCs, many of the existing cone BCs models are assumed to be passive or only contain calcium channels at the synaptic terminals. We have utilized our Admittance Method (AM)-NEURON computational platform to implement a more realistic model of ON-BCs. Our model closely replicates the recent patch-clamp experiments directly measuring the response of ON-BCs to epiretinal electrical stimulation and thereby predicts the regional distributions of the ionic channels. Our computational results further indicate that outward potassium current strongly contributes to the depolarizing voltage transient of ON-BCs in response to electrical stimulation.more » « less
-
The endoplasmic reticulum (ER) forms a continuous and dynamic network throughout a neuron, extending from dendrites to axon terminals, and axonal ER dysfunction is implicated in several neurological disorders. In addition, tight junctions between the ER and plasma membrane (PM) are formed by several molecules including Kv2 channels, but the cellular functions of many ER-PM junctions remain unknown. Recently, dynamic Ca 2+ uptake into the ER during electrical activity was shown to play an essential role in synaptic transmission. Our experiments demonstrate that Kv2.1 channels are necessary for enabling ER Ca 2+ uptake during electrical activity, as knockdown (KD) of Kv2.1 rendered both the somatic and axonal ER unable to accumulate Ca 2+ during electrical stimulation. Moreover, our experiments demonstrate that the loss of Kv2.1 in the axon impairs synaptic vesicle fusion during stimulation via a mechanism unrelated to voltage. Thus, our data demonstrate that a nonconducting role of Kv2.1 exists through its binding to the ER protein VAMP-associated protein (VAP), which couples ER Ca 2+ uptake with electrical activity. Our results further suggest that Kv2.1 has a critical function in neuronal cell biology for Ca 2+ handling independent of voltage and reveals a critical pathway for maintaining ER lumen Ca 2+ levels and efficient neurotransmitter release. Taken together, these findings reveal an essential nonclassical role for both Kv2.1 and the ER-PM junctions in synaptic transmission.more » « less
An official website of the United States government

