scholarly journals NMDA receptors enhance the fidelity of synaptic integration

2019 ◽  
Author(s):  
Chenguang Li ◽  
Allan T. Gulledge
Keyword(s):  
Membrane Potential ◽  
Nmda Receptors ◽  
Synaptic Input ◽  
Voltage Dependence ◽  
Membrane Potentials ◽  
Synaptic Integration ◽  
Receptor Subtypes ◽  
Dendritic Location ◽  
Initial Membrane ◽  
Ampa And Nmda Receptors

AbstractExcitatory synaptic transmission in many neurons is mediated by two co-expressed ionotropic glutamate receptor subtypes, AMPA and NMDA receptors, that differ in their kinetics, ion-selectivity, and voltage-sensitivity. AMPA receptors have fast kinetics and are voltage-insensitive, while NMDA receptors have slower kinetics and increased conductance at depolarized membrane potentials. Here we report that the voltage-dependency and kinetics of NMDA receptors act synergistically to stabilize synaptic integration of excitatory postsynaptic potentials (EPSPs) across spatial and voltage domains. Simulations of synaptic integration in simplified and morphologically realistic dendritic trees revealed that the combined presence of AMPA and NMDA conductances reduces the variability of somatic responses to spatiotemporal patterns of excitatory synaptic input presented at different initial membrane potentials and/or in different dendritic domains. This moderating effect of the NMDA conductance on synaptic integration was robust across a wide range of AMPA-to-NMDA ratios, and results from synergistic interaction of NMDA kinetics (which reduces variability across membrane potential) and voltage-dependence (which favors stabilization across dendritic location). When combined with AMPA conductance, the NMDA conductance balances voltage- and impedance-dependent changes in synaptic driving force, and distance-dependent attenuation of synaptic potentials arriving at the axon, to increase the fidelity of synaptic integration and EPSP-spike coupling across neuron state (i.e., initial membrane potential) and dendritic location of synaptic input. Thus, synaptic NMDA receptors convey advantages for synaptic integration that are independent of, but fully compatible with, their importance for coincidence detection and synaptic plasticity.Significance StatementGlutamate is an excitatory neurotransmitter that, at many synapses, gates two coexpressed receptor subtypes (AMPA and NMDA receptors). Computational simulations reveal that the combined synaptic presence of AMPA and NMDA receptors reduces variability in synaptic integration in response to identical patterns of synaptic input delivered to different dendritic locations and/or at different initial membrane potentials. This results from synergistic interaction of the slower kinetics and voltage-dependence of NMDA receptors, which combine to enhance synaptic currents when synaptic driving forces are otherwise reduced (e.g., at depolarized membrane potentials or in distal, high-impedance dendrites). By stabilizing synaptic integration across dendritic location and initial membrane potential, NMDA receptors provide advantages independent of, but fully compatible with, their well-known contribution to synaptic plasticity.

scholarly journals Tracking S4 movement by gating pore currents in the bacterial sodium channel NaChBac

2014 ◽  
Vol 144 (2) ◽  
pp. 147-157 ◽  
Author(s):  
Tamer M. Gamal El-Din ◽  
Todd Scheuer ◽  
William A. Catterall
Keyword(s):  
Membrane Potential ◽  
Sodium Channel ◽  
Sodium Channels ◽  
Voltage Dependence ◽  
Periodic Paralysis ◽  
Membrane Potentials ◽  
Structural Basis ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Gating Charges

Voltage-gated sodium channels mediate the initiation and propagation of action potentials in excitable cells. Transmembrane segment S4 of voltage-gated sodium channels resides in a gating pore where it senses the membrane potential and controls channel gating. Substitution of individual S4 arginine gating charges (R1–R3) with smaller amino acids allows ionic currents to flow through the mutant gating pore, and these gating pore currents are pathogenic in some skeletal muscle periodic paralysis syndromes. The voltage dependence of gating pore currents provides information about the transmembrane position of the gating charges as S4 moves in response to membrane potential. Here we studied gating pore current in mutants of the homotetrameric bacterial sodium channel NaChBac in which individual arginine gating charges were replaced by cysteine. Gating pore current was observed for each mutant channel, but with different voltage-dependent properties. Mutating the first (R1C) or second (R2C) arginine to cysteine resulted in gating pore current at hyperpolarized membrane potentials, where the channels are in resting states, but not at depolarized potentials, where the channels are activated. Conversely, the R3C gating pore is closed at hyperpolarized membrane potentials and opens with channel activation. Negative conditioning pulses revealed time-dependent deactivation of the R3C gating pore at the most hyperpolarized potentials. Our results show sequential voltage dependence of activation of gating pore current from R1 to R3 and support stepwise outward movement of the substituted cysteines through the narrow portion of the gating pore that is sealed by the arginine side chains in the wild-type channel. This pattern of voltage dependence of gating pore current is consistent with a sliding movement of the S4 helix through the gating pore. Through comparison with high-resolution models of the voltage sensor of bacterial sodium channels, these results shed light on the structural basis for pathogenic gating pore currents in periodic paralysis syndromes.

Voltage dependence of membrane properties of trigeminal root ganglion neurons

1987 ◽  
Vol 58 (1) ◽  
pp. 66-86 ◽  
Author(s):  
E. Puil ◽  
B. Gimbarzevsky ◽  
R. M. Miura
Keyword(s):  
Membrane Potential ◽  
Voltage Dependence ◽  
Complex Impedance ◽  
Membrane Potentials ◽  
Membrane Properties ◽  
Resonant Peak ◽  
Impedance Data ◽  
Trigeminal Root ◽  
Ganglion Neurons ◽  
Impedance Magnitude

1. Membrane potentials of trigeminal root ganglion neurons were varied systematically by intracellular injections of long-lasting step currents to determine the voltage dependence of their membrane electrical properties. The complex impedance and impedance magnitude functions were first determined using oscillatory input currents superimposed on these step currents. 2. Systematic step variations in the membrane potential led to qualitative changes in the impedance magnitude functions. Depolarization of neurons exhibiting resonance at their initial resting membrane potentials resulted in a reduction in the resonance behavior. Hyperpolarization of these neurons to membrane potentials of about -80 to -90 mV led to a disappearance of the resonant peak but increased the maximum of the impedance magnitude. 3. The complex impedance data were fitted with a neuronal model derived from linearized Hodgkin-Huxley-like equations, yielding estimates for the membrane properties. The four parameters of the model were 1) a time invariant, resting membrane conductance, Gr, 2) a voltage- and time-dependent conductance, GL, 3) a time constant, tau u, for the unknown ionic channels that are activated by the 2- to 5-mV oscillatory perturbation of the stepped membrane potential, and 4) Ci, the input capacitance. 4. The results of the curve-fitting procedures suggested that all parameters depended on membrane voltage. The most voltage-dependent parameters were GL and tau u throughout a 25- to 30-mV range that was subthreshold to the production of action potentials. Both Gr and GL increased with subthreshold depolarization. 5. These impedance data suggest the very important role of the membrane potential of the trigeminal root ganglion neurons on their abilities to synthesize and filter inputted electrical signals.

scholarly journals Impact of subthreshold membrane potential on synaptic responses at dendritic spines of layer 5 pyramidal neurons in the prefrontal cortex

2014 ◽  
Vol 111 (10) ◽  
pp. 1960-1972 ◽  
Author(s):  
Hannah J. Seong ◽  
Rudy Behnia ◽  
Adam G. Carter
Keyword(s):  
Prefrontal Cortex ◽  
Membrane Potential ◽  
Nmda Receptors ◽  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
K Channels ◽  
Two Photon ◽  
Synaptic Potentials ◽  
Ampa And Nmda Receptors ◽  
Synaptic Responses

Glutamatergic inputs onto cortical pyramidal neurons are received and initially processed at dendritic spines. AMPA and NMDA receptors generate both synaptic potentials and calcium (Ca) signals in the spine head. These responses can in turn activate a variety of Ca, sodium (Na), and potassium (K) channels at spines. In principle, the roles of these receptors and channels can be strongly regulated by the subthreshold membrane potential. However, the impact of different receptors and channels has usually been studied at the level of dendrites. Much less is known about their influence at spines, where synaptic transmission and plasticity primarily occur. Here we examine single-spine responses in the basal dendrites of layer 5 pyramidal neurons in the mouse prefrontal cortex. Using two-photon microscopy and two-photon uncaging, we first show that synaptic potentials and Ca signals differ at resting and near-threshold potentials. We then determine how subthreshold depolarizations alter the contributions of AMPA and NMDA receptors to synaptic responses. We show that voltage-sensitive Ca channels enhance synaptic Ca signals but fail to engage small-conductance Ca-activated K (SK) channels, which require greater numbers of inputs. Finally, we establish how the subthreshold membrane potential controls the ability of voltage-sensitive Na channels and K channels to influence synaptic responses. Our findings reveal how subthreshold depolarizations promote electrical and biochemical signaling at dendritic spines by regulating the contributions of multiple glutamate receptors and ion channels.

scholarly journals Noninactivating tension in rat skeletal muscle. Effects of thyroid hormone.

1989 ◽  
Vol 94 (1) ◽  
pp. 183-203 ◽  
Author(s):  
M Chua ◽  
A F Dulhunty
Keyword(s):  
Skeletal Muscle ◽  
Steady State ◽  
Membrane Potential ◽  
Extensor Digitorum Longus ◽  
Voltage Dependence ◽  
Surface Membrane ◽  
Membrane Potentials ◽  
Resting Membrane Potential ◽  
Rat Skeletal Muscle ◽  
Contraction Coupling

Inactivation of excitation-contraction coupling was examined in extensor digitorum longus (EDL) and soleus muscle fibers from rats injected daily with tri-iodothyronine (T3, 150 micrograms/kg) for 10-14 d. Steady-state activation and inactivation curves for contraction were obtained from measurements of peak potassium contracture tension at different surface membrane potentials. The experiments tested the hypothesis that noninactivating tension is a "window" tension caused by the overlap of the activation and inactivation curves. Changes in the amplitude and voltage dependence of noninactivating tension should be predicted by the changes in the activation and inactivation curves, if noninactivating tension arises from their overlap. After T3 treatment, the area of overlap increased in EDL fibers and decreased in soleus fibers and the overlap region was shifted to more negative potentials in both muscles. Noninactivating tension also appeared at more negative membrane potentials after T3 treatment in both EDL and soleus fibers. The effects of T3 treatment were confirmed with a two microelectrode voltage-clamp technique: at the resting membrane potential (-80 mV) contraction in response to a brief test pulse required less than normal depolarization in EDL, but more than normal depolarization in soleus fibers. After T3 treatment, the increase in contraction threshold at depolarized holding potentials (attributed to inactivation) occurred at more depolarized holding potentials in EDL, or less depolarized holding potentials in soleus. The changes in contraction threshold could be accounted for by the effects of T3 on the activation and inactivation curves. In conclusion, (a) T3 appeared to affect the expression of both activation and inactivation characteristics, but the activation effects could not be cleanly distinguished from T3 effects on the sarcoplasmic reticulum and contractile proteins, and (b) the experiments provided evidence for the hypothesis that the noninactivating tension is a steady-state "window" tension.

scholarly journals On the Wireless Microwave Sensing of Bacterial Membrane Potential in Microfluidic-Actuated Platforms

Sensors ◽  
2021 ◽  
Vol 21 (10) ◽  
pp. 3420
Author(s):  
Marc Jofre ◽  
Lluís Jofre ◽  
Luis Jofre-Roca
Keyword(s):  
Membrane Potential ◽  
Living Cells ◽  
Membrane Potentials ◽  
Electromagnetic Properties ◽  
Bacterial Membrane ◽  
Microfluidic Platforms ◽  
Bacterial Membranes ◽  
Wireless Monitoring ◽  
Bacterial Dynamics ◽  
Engineered Systems

The investigation of the electromagnetic properties of biological particles in microfluidic platforms may enable microwave wireless monitoring and interaction with the functional activity of microorganisms. Of high relevance are the action and membrane potentials as they are some of the most important parameters of living cells. In particular, the complex mechanisms of a cell’s action potential are comparable to the dynamics of bacterial membranes, and consequently focusing on the latter provides a simplified framework for advancing the current techniques and knowledge of general bacterial dynamics. In this work, we provide a theoretical analysis and experimental results on the microwave detection of microorganisms within a microfluidic-based platform for sensing the membrane potential of bacteria. The results further advance the state of microwave bacteria sensing and microfluidic control and their implications for measuring and interacting with cells and their membrane potentials, which is of great importance for developing new biotechnologically engineered systems and solutions.

scholarly journals Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rongkang Deng ◽  
Joseph P. Y. Kao ◽  
Patrick O. Kanold
Keyword(s):  
Visual Cortex ◽  
Nmda Receptors ◽  
Laser Scanning ◽  
Inhibitory Neurons ◽  
Gabaergic Interneurons ◽  
Cortical Circuits ◽  
Retinal Input ◽  
Layer 4 ◽  
Ampa And Nmda Receptors ◽  
Laser Scanning Photostimulation

AbstractThe development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical circuits. These glutamatergic connections are mediated by glutamate receptors including AMPA and NMDA receptors and the ratio of AMPA to NMDA receptors decreases during development. Since previous studies have shown that retinal input can regulate the early development of connections along the visual pathway, we investigated if the maturation of glutamatergic inputs to GABAergic interneurons in the visual cortex requires retinal input. We mapped the spatial pattern of glutamatergic connections to layer 4 (L4) GABAergic interneurons in mouse visual cortex at around postnatal day (P) 16 by laser-scanning photostimulation and investigated the effect of binocular enucleations at P1/P2 on these patterns. Gad2-positive interneurons in enucleated animals showed an increased fraction of AMPAR-mediated input from L2/3 and a decreased fraction of input from L5/6. Parvalbumin-expressing (PV) interneurons showed similar changes in relative connectivity. NMDAR-only input was largely unchanged by enucleation. Our results show that retinal input sculpts the integration of interneurons into V1 circuits and suggest that the development of AMPAR- and NMDAR-only connections might be regulated differently.

A Fast Synaptic Potential Mediated by NMDA and Non-NMDA Receptors

1997 ◽  
Vol 78 (5) ◽  
pp. 2693-2706 ◽  
Author(s):  
Laura R. Wolszon ◽  
Alberto E. Pereda ◽  
Donald S. Faber
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Resting Potential ◽  
Repetitive Firing ◽  
Physiological Data ◽  
Receptor Subtypes ◽  
Excitatory Postsynaptic Potential ◽  
Synaptic Potential ◽  
Synaptic Currents ◽  
Fast Kinetics

Wolszon, Laura R., Alberto E. Pereda, and Donald S. Faber. A fast synaptic potential mediated by NMDA and non-NMDA receptors. J. Neurophysiol. 78: 2693–2706, 1997. Excitatory synaptic transmission in the CNS often is mediated by two kinetically distinct glutamate receptor subtypes that frequently are colocalized, the N-methyl-d-aspartate (NMDA) and non-NMDA receptors. Their synaptic currents are typically very slow and very fast, respectively. We examined the pharmacological and physiological properties of chemical excitatory transmission at the mixed electrical and chemical synapses between auditory afferents and the goldfish Mauthner cell, in vivo. Previous physiological data have suggested the involvement of glutamate receptors in this fast excitatory postsynaptic potential (EPSP), the chemical component of which decays with a time constant of <2 ms. We demonstrate here that the pharmacological and voltage-dependent characteristics of the synaptic currents are consistent with glutamatergic transmission and that both NMDA and non-NMDA receptors are involved. The two components surprisingly exhibit quite similar kinetics even at resting potential, with the NMDA response being only slightly slower. Due to its fast kinetics and characteristic voltage dependence, NMDA receptor-mediated transmission at these first-order synapses contributes significantly to paired pulse and frequency-dependent facilitation of successive fast EPSPs during high-frequency repetitive firing, a presynaptic impulse pattern that induces activity-dependent homosynaptic changes in both electrical and chemical transmission. Thus NMDA receptor kinetics in this intact preparation are suited to its functional requirements, namely speed of information transmission and the ability to trigger changes in synaptic efficacy.

Voltage-Dependent Properties of Dendrites That Eliminate Location-Dependent Variability of Synaptic Input

1999 ◽  
Vol 81 (2) ◽  
pp. 535-543 ◽  
Author(s):  
Erik P. Cook ◽  
Daniel Johnston
Keyword(s):  
Synaptic Input ◽  
Outward Current ◽  
Compartment Model ◽  
Inward Current ◽  
Voltage Gated ◽  
Cable Properties ◽  
Dendritic Membrane ◽  
Voltage Dependent ◽  
Dendritic Location ◽  
Voltage Gated Channels

Voltage-dependent properties of dendrites that eliminate location-dependent variability of synaptic input. We examined the hypothesis that voltage-dependent properties of dendrites allow for the accurate transfer of synaptic information to the soma independent of synapse location. This hypothesis is motivated by experimental evidence that dendrites contain a complex array of voltage-gated channels. How these channels affect synaptic integration is unknown. One hypothesized role for dendritic voltage-gated channels is to counteract passive cable properties, rendering all synapses electrotonically equidistant from the soma. With dendrites modeled as passive cables, the effect a synapse exerts at the soma depends on dendritic location (referred to as location-dependent variability of the synaptic input). In this theoretical study we used a simplified three-compartment model of a neuron to determine the dendritic voltage-dependent properties required for accurate transfer of synaptic information to the soma independent of synapse location. A dendrite that eliminates location-dependent variability requires three components: 1) a steady-state, voltage-dependent inward current that together with the passive leak current provides a net outward current and a zero slope conductance at depolarized potentials, 2) a fast, transient, inward current that compensates for dendritic membrane capacitance, and 3) both αamino-3-hydroxy-5-methyl-4-isoxazolepropionic acid– and N-methyl-d-aspartate–like synaptic conductances that together permit synapses to behave as ideal current sources. These components are consistent with the known properties of dendrites. In addition, these results indicate that a dendrite designed to eliminate location-dependent variability also actively back-propagates somatic action potentials.

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