scholarly journals Comparison of the Inhibition of Renshaw Cells During Subthreshold and Suprathreshold Conditions Using Anatomically and Physiologically Realistic Models

2005 ◽  
Vol 94 (3) ◽  
pp. 1688-1698 ◽  
Author(s):  
Tuan V. Bui ◽  
Dianne E. Dewey ◽  
Robert E. W. Fyffe ◽  
P. Ken Rose
Keyword(s):  
Voltage Clamp ◽  
Relative Effectiveness ◽  
Operating Conditions ◽  
Synaptic Activity ◽  
Inhibitory Synapses ◽  
Renshaw Cells ◽  
Effective Inhibition ◽  
Voltage Clamping ◽  
Recurrent Collaterals ◽  
Excitatory Drive

Inhibitory synaptic inputs to Renshaw cells are concentrated on the soma and the juxtasomatic dendrites. In the present study, we investigated whether this proximal bias leads to more effective inhibition under different neuronal operating conditions. Using compartmental models based on detailed anatomical measurements of intracellularly stained Renshaw cells, we compared the inhibition produced by glycine/γ-aminobutyric acid-A (GABAA) synapses when distributed with a proximal bias to the inhibition produced when the same synapses were distributed uniformly (i.e., with no regional bias). The comparison was conducted in subthreshold and suprathreshold conditions. The latter were mimicked by voltage clamping the soma to −55 mV. The voltage clamp reduces nonlinear interactions between excitatory and inhibitory synapses. We hypothesized that for electrotonically compact cells such as Renshaw cells, the strength of the inhibition would become much less dependent on synaptic location in suprathreshold conditions. This hypothesis was not confirmed. The inhibition produced when inhibitory inputs were proximally distributed was always stronger than when the same inputs were uniformly distributed. In fact, the relative effectiveness of proximally distributed inhibitory inputs over uniformly distributed synapses was greater in suprathreshold conditions than that in subthreshold conditions. The somatic voltage clamp minimized saturation of inhibitory driving potentials. Because this effect was greatest near the soma, the current produced by more distal synapses suffered a greater loss because of saturation. Conversely, in subthreshold conditions, the effectiveness of proximal synapses was substantially reduced at high levels of background synaptic activity because of saturation. Our results suggest glycine/GABAA synapses on Renshaw cells are strategically distributed to block the powerful excitatory drive produced by recurrent collaterals from motoneurons.

Properties of Renshaw cells excited by recurrent collaterals of pudendal motoneurons in the cat

2009 ◽  
Vol 65 ◽  
pp. S167
Author(s):  
Ken Muramatsu ◽  
Masatoshi Niwa ◽  
Kenji Sato ◽  
Sei-Ichi Sasaki
Keyword(s):  
Renshaw Cells ◽  
Recurrent Collaterals

scholarly journals Enhanced dynamic voltage clamping capability of Clustered IGBT at turn-off period

2016 ◽  
Vol 29 (1) ◽  
pp. 1-10
Author(s):  
Hong Long ◽  
Mark Sweet ◽  
Sankara Narayanan
Keyword(s):  
Numerical Evaluation ◽  
Load Condition ◽  
Operating Conditions ◽  
Current Gain ◽  
Power Devices ◽  
Inductive Load ◽  
Dynamic Voltage ◽  
Voltage Clamping ◽  
Safe Operating ◽  
Off Time

One of the critical requirements for high power devices is to have rugged and reliable capability against hash operating conditions. In this paper, we present the dynamic voltage clamping capability of 3.3kV Field Stop Clustered IGBT devices under extreme inductive load condition. It shows that PMOS trench gate CIGBT structure with outstanding performance of fast turn-off time and low over-shoot voltage. Further optimization of current gain of CIGBT structure is analyzed through numerical evaluation. A step further in the safe operating area has been achieved for high voltage devices by CIGBT technology.

Facilitated Glutamatergic Transmission in the Striatum of D2 Dopamine Receptor-Deficient Mice

2001 ◽  
Vol 85 (2) ◽  
pp. 659-670 ◽  
Author(s):  
C. Cepeda ◽  
R. S. Hurst ◽  
K. L. Altemus ◽  
J. Flores-Hernández ◽  
C. R. Calvert ◽  
...  
Keyword(s):  
Voltage Clamp ◽  
Glutamate Receptor ◽  
Excitatory Amino Acid ◽  
Glutamate Release ◽  
Synaptic Activity ◽  
Membrane Properties ◽  
Receptor Subtype ◽  
Da Receptors ◽  
Change In Mean ◽  
Deficient Mice

Dopamine (DA) receptors play an important role in the modulation of excitability and the responsiveness of neurons to activation of excitatory amino acid receptors in the striatum. In the present study, we utilized mice with genetic deletion of D2 or D4 DA receptors and their wild-type (WT) controls to examine if the absence of either receptor subtype affects striatal excitatory synaptic activity. Immunocytochemical analysis verified the absence of D2 or D4 protein expression in the striatum of receptor-deficient mutant animals. Sharp electrode current- and whole cell patch voltage-clamp recordings were obtained from slices of receptor-deficient and WT mice. Basic membrane properties were similar in D2 and D4 receptor-deficient mutants and their respective WT controls. In current-clamp recordings in WT animals, very little low-amplitude spontaneous synaptic activity was observed. The frequency of these spontaneous events was increased slightly in D2 receptor-deficient mice. In addition, large-amplitude depolarizations were observed in a subset of neurons from only the D2 receptor-deficient mutants. Bath application of the K+ channel blocker 4-aminopyridine (100 μM) and bicuculline methiodide (10 μM, to block synaptic activity due to activation of GABAA receptors) markedly increased spontaneous synaptic activity in receptor-deficient mutants and WTs. Under these conditions, D2 receptor-deficient mice displayed significantly more excitatory synaptic activity than their WT controls, while there was no difference between D4receptor-deficient mice and their controls. In voltage-clamp recordings, there was an increase in frequency of spontaneous glutamate receptor-mediated inward currents without a change in mean amplitude in D2 receptor-deficient mutants. In WT mice, activation of D2 family receptors with quinpirole decreased spontaneous excitatory events and conversely sulpiride, a D2 receptor antagonist, increased activity. In D2 receptor-deficient mice, sulpiride had very little net effect. Morphologically, a subpopulation of medium-sized spiny neurons from D2 receptor-deficient mice displayed decreased dendritic spines compared with cells from WT mice. These results provide evidence that D2 receptors play an important role in the regulation of glutamate receptor-mediated activity in the corticostriatal or thalamostriatal pathway. These receptors may function as gatekeepers of glutamate release or of its subsequent effects and thus may protect striatal neurons from excessive excitation.

Space-Clamp Problems When Voltage Clamping Neurons Expressing Voltage-Gated Conductances

2008 ◽  
Vol 99 (3) ◽  
pp. 1127-1136 ◽  
Author(s):  
Dan Bar-Yehuda ◽  
Alon Korngreen
Keyword(s):  
Voltage Clamp ◽  
Reversal Potential ◽  
Voltage Gated ◽  
Cable Theory ◽  
Local Current ◽  
Branching Neurons ◽  
Potential Decay ◽  
Voltage Clamping ◽  
Rat Somatosensory Cortex ◽  
Spherical Cells

The voltage-clamp technique is applicable only to spherical cells. In nonspherical cells, such as neurons, the membrane potential is not clamped distal to the voltage-clamp electrode. This means that the current recorded by the voltage-clamp electrode is the sum of the local current and of axial currents from locations experiencing different membrane potentials. Furthermore, voltage-gated currents recorded from a nonspherical cell are, by definition, severely distorted due to the lack of space clamp. Justifications for voltage clamping in nonspherical cells are, first, that the lack of space clamp is not severe in neurons with short dendrites. Second, passive cable theory may be invoked to justify application of voltage clamp to branching neurons, suggesting that the potential decay is sufficiently shallow to allow spatial clamping of the neuron. Here, using numerical simulations, we show that the distortions of voltage-gated K+ and Ca2+ currents are substantial even in neurons with short dendrites. The simulations also demonstrate that passive cable theory cannot be used to justify voltage clamping of neurons due to significant shunting to the reversal potential of the voltage-gated conductance during channel activation. Some of the predictions made by the simulations were verified using somatic and dendritic voltage-clamp experiments in rat somatosensory cortex. Our results demonstrate that voltage-gated K+ and Ca2+ currents recorded from branching neurons are almost always severely distorted.

Two Dynamically Distinct Inhibitory Networks in Layer 4 of the Neocortex

2003 ◽  
Vol 90 (5) ◽  
pp. 2987-3000 ◽  
Author(s):  
Michael Beierlein ◽  
Jay R. Gibson ◽  
Barry W. Connors
Keyword(s):  
Barrel Cortex ◽  
Dynamic Properties ◽  
Inhibitory Synapses ◽  
Projection Neurons ◽  
Inhibitory Interneurons ◽  
Short Term ◽  
Layer 4 ◽  
Recurrent Collaterals ◽  
Chemical Synapses ◽  
Excitatory And Inhibitory Synapses

Normal operations of the neocortex depend critically on several types of inhibitory interneurons, but the specific function of each type is unknown. One possibility is that interneurons are differentially engaged by patterns of activity that vary in frequency and timing. To explore this, we studied the strength and short-term dynamics of chemical synapses interconnecting local excitatory neurons (regular-spiking, or RS, cells) with two types of inhibitory interneurons: fast-spiking (FS) cells, and low-threshold spiking (LTS) cells of layer 4 in the rat barrel cortex. We also tested two other pathways onto the interneurons: thalamocortical connections and recurrent collaterals from corticothalamic projection neurons of layer 6. The excitatory and inhibitory synapses interconnecting RS cells and FS cells were highly reliable in response to single stimuli and displayed strong short-term depression. In contrast, excitatory and inhibitory synapses interconnecting the RS and LTS cells were less reliable when initially activated. Excitatory synapses from RS cells onto LTS cells showed dramatic short-term facilitation, whereas inhibitory synapses made by LTS cells onto RS cells facilitated modestly or slightly depressed. Thalamocortical inputs strongly excited both RS and FS cells but rarely and only weakly contacted LTS cells. Both types of interneurons were strongly excited by facilitating synapses from axon collaterals of corticothalamic neurons. We conclude that there are two parallel but dynamically distinct systems of synaptic inhibition in layer 4 of neocortex, each defined by its intrinsic spiking properties, the short-term plasticity of its chemical synapses, and (as shown previously) an exclusive set of electrical synapses. Because of their unique dynamic properties, each inhibitory network will be recruited by different temporal patterns of cortical activity.

scholarly journals Selective impact of MeCP2 and associated histone deacetylases on the dynamics of evoked excitatory neurotransmission

2011 ◽  
Vol 106 (1) ◽  
pp. 193-201 ◽  
Author(s):  
Erika D. Nelson ◽  
Manjot Bal ◽  
Ege T. Kavalali ◽  
Lisa M. Monteggia
Keyword(s):  
Histone Deacetylases ◽  
Hippocampal Neurons ◽  
Autism Spectrum ◽  
Synaptic Activity ◽  
Short Term ◽  
Histone Deacetylase 1 ◽  
Inhibitory Neurotransmission ◽  
Presynaptic Release ◽  
Excitatory Neurotransmission ◽  
Excitatory Drive

An imbalance between the strengths of excitatory and inhibitory synaptic inputs has been proposed as the cellular basis of autism and related neurodevelopmental disorders. Previous studies examining spontaneous levels of excitatory and inhibitory neurotransmission in the forebrain regions of methyl-CpG-binding protein 2 ( Mecp2) mutant mice, models of the autism spectrum disorder Rett syndrome, have identified a decrease in excitatory drive, in some cases coupled with an increase in inhibitory synaptic strength, as a major source of this imbalance. Here, we reevaluated this question by examining the short-term dynamics of evoked neurotransmission between hippocampal neurons cultured from MeCP2 knockout mice and found a marked increase in evoked excitatory neurotransmission that is consistent with an increase in presynaptic release probability. This increase in evoked excitatory drive was not matched with alterations in evoked inhibitory neurotransmission. Moreover, we observed similar excitatory drive specific changes after the loss of key histone deacetylases (histone deacetylase 1 and 2) that form a complex with MeCP2 and mediate transcriptional regulation. These findings suggest a distinct role for MeCP2 and its cofactors in the regulation of evoked excitatory neurotransmission compared with their essential role in basal synaptic activity.

scholarly journals Neuroligins/LRRTMs prevent activity- and Ca2+/calmodulin-dependent synapse elimination in cultured neurons

2011 ◽  
Vol 194 (2) ◽  
pp. 323-334 ◽  
Author(s):  
Jaewon Ko ◽  
Gilberto J. Soler-Llavina ◽  
Marc V. Fuccillo ◽  
Robert C. Malenka ◽  
Thomas C. Südhof
Keyword(s):  
Hippocampal Neurons ◽  
Transmembrane Proteins ◽  
Synaptic Activity ◽  
Inhibitory Synapses ◽  
Excitatory Synapses ◽  
Synapse Elimination ◽  
Synapse Loss ◽  
A Cell ◽  
Dependent Signaling Pathway ◽  
Cultured Hippocampal Neurons

Neuroligins (NLs) and leucine-rich repeat transmembrane proteins (LRRTMs) are postsynaptic cell adhesion molecules that bind to presynaptic neurexins. In this paper, we show that short hairpin ribonucleic acid–mediated knockdowns (KDs) of LRRTM1, LRRTM2, and/or NL-3, alone or together as double or triple KDs (TKDs) in cultured hippocampal neurons, did not decrease synapse numbers. In neurons cultured from NL-1 knockout mice, however, TKD of LRRTMs and NL-3 induced an ∼40% loss of excitatory but not inhibitory synapses. Strikingly, synapse loss triggered by the LRRTM/NL deficiency was abrogated by chronic blockade of synaptic activity as well as by chronic inhibition of Ca2+ influx or Ca2+/calmodulin (CaM) kinases. Furthermore, postsynaptic KD of CaM prevented synapse loss in a cell-autonomous manner, an effect that was reversed by CaM rescue. Our results suggest that two neurexin ligands, LRRTMs and NLs, act redundantly to maintain excitatory synapses and that synapse elimination caused by the absence of NLs and LRRTMs is promoted by synaptic activity and mediated by a postsynaptic Ca2+/CaM-dependent signaling pathway.

scholarly journals Inhibitory-excitatory synaptic balance is shifted toward increased excitation in magnocellular neurosecretory cells of heart failure rats

2011 ◽  
Vol 106 (3) ◽  
pp. 1545-1557 ◽  
Author(s):  
Evgeniy S. Potapenko ◽  
Vinicia C. Biancardi ◽  
Renea M. Florschutz ◽  
Pan D. Ryu ◽  
Javier E. Stern
Keyword(s):  
Heart Failure ◽  
Ampa Receptor ◽  
Time Course ◽  
Neurosecretory Cell ◽  
Brain Slices ◽  
Synaptic Strength ◽  
Neurosecretory Cells ◽  
Synaptic Function ◽  
Synaptic Activity ◽  
Excitatory Drive

Despite the well-established contribution of neurohumoral activation to morbidity and mortality in heart failure (HF) patients, relatively little is known about the underlying central nervous system mechanisms. In this study, we aimed to determine whether changes in GABAergic inhibitory and glutamatergic excitatory synaptic function contribute to altered hypothalamic magnocellular neurosecretory cell (MNC) activity in HF rats. Patch-clamp recordings were obtained from MNCs in brain slices from sham and HF rats. Glutamate excitatory (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs) were simultaneously recorded, and changes in their strengths, as well as their interactions, were evaluated. We found a diminished GABAergic synaptic strength in MNCs of HF rats, reflected as faster decaying IPSCs and diminished mean IPSC charge transfer. Opposite changes were observed in glutamate EPSC synaptic strength, resulting in a shift in the GABA-glutamate balance toward a relatively stronger glutamate influence in HF rats. The prolongation of glutamate EPSCs during HF was mediated, at least in part, by an enhanced contribution of AMPA receptor desensitization to the EPSC decay time course. EPSC prolongation, and consequently increased unitary strength, resulted in a stronger AMPA receptor-mediated excitatory drive to firing discharge in MNCs of HF rats. Blockade of GABAA synaptic activity diminished the EPSC waveform variability observed among events in sham rats, an effect that was blunted in HF rats. Together, our results suggest that opposing changes in postsynaptic properties of GABAergic and glutamatergic synaptic function contribute to enhanced magnocellular neurosecretory activity in HF rats.

scholarly journals Relative Location of Inhibitory Synapses and Persistent Inward Currents Determines the Magnitude and Mode of Synaptic Amplification in Motoneurons

2008 ◽  
Vol 99 (2) ◽  
pp. 583-594 ◽  
Author(s):  
Tuan V. Bui ◽  
Giovanbattista Grande ◽  
P. Ken Rose
Keyword(s):  
Hot Spots ◽  
Nonuniform Distribution ◽  
Inhibitory Synapses ◽  
Renshaw Cells ◽  
Relative Location ◽  
Persistent Inward Currents ◽  
Synaptic Inputs ◽  
Renshaw Cell ◽  
Inward Currents ◽  
Cell Synapse

In some motoneurons, L-type Ca2+ channels that partly mediate persistent inward currents (PICs) have been estimated to be arranged in 50- to 200-μm-long discrete regions in the dendrites, centered 100 to 400 μm from the soma. As a consequence of this nonuniform distribution, the interaction between synaptic inputs to motoneurons and these channels may vary according to the distribution of the synapses. For instance, >93% of synapses from Renshaw cells have been observed to be located 65 to 470 μm away from the cell body of motoneurons. Our goal was to assess whether Renshaw cell synapses are distributed in a position to more effectively control the activation of the L-type Ca2+ channels. Using compartmental models of motoneurons with L-type Ca2+ channels distributed in 100-μm-long hot spots centered 100 to 400 μm away from the soma, we compared the inhibition generated by four distributions of inhibitory synapses: proximal, distal, uniform, and one based on the location of Renshaw cell synapses on motoneurons. Regardless of whether the synapses were activated tonically or transiently, in the presence of L-type Ca2+ channels, inhibitory synapses distributed according to the Renshaw cell synapse distribution generate the largest inhibitory currents. The effectiveness of a particular distribution of inhibitory synapses in the presence of PICs depends on their ability to deactivate the channels underlying PICs, which is influenced not only by the superposition between synapses and channels, but also by the distance away from the somatic voltage clamp.

Effect of Nonlinear Summation of Synaptic Currents on the Input–Output Properties of Spinal Motoneurons

2005 ◽  
Vol 94 (5) ◽  
pp. 3465-3478 ◽  
Author(s):  
S. Cushing ◽  
T. Bui ◽  
P. K. Rose
Keyword(s):  
Synaptic Activity ◽  
Inhibitory Synapses ◽  
Excitatory Synapses ◽  
Input Output ◽  
Highly Nonlinear ◽  
Intrinsic Nonlinearity ◽  
Motoneuron Activity ◽  
The Impact ◽  
Driving Potential ◽  
Excitatory And Inhibitory Synapses

A single spinal motoneuron receives tens of thousands of synapses. The neurotransmitters released by many of these synapses act on iontotropic receptors and alter the driving potential of neighboring synapses. This interaction introduces an intrinsic nonlinearity in motoneuron input–output properties where the response to two simultaneous inputs is less than the linear sum of the responses to each input alone. Our goal was to determine the impact of this nonlinearity on the current delivered to the soma during activation of predetermined numbers and distributions of excitatory and inhibitory synapses. To accomplish this goal we constructed compartmental models constrained by detailed measurements of the geometry of the dendritic trees of three feline motoneurons. The current “lost” as a result of local changes in driving potential was substantial and resulted in a highly nonlinear relationship between the number of active synapses and the current reaching the soma. Background synaptic activity consisting of a balanced activation of excitatory and inhibitory synapses further decreased the current delivered to the soma, but reduced the nonlinearity with respect to the total number of active excitatory synapses. Unexpectedly, simulations that mimicked experimental measures of nonlinear summation, activation of two sets of excitatory synapses, resulted in nearly linear summation. This result suggests that nonlinear summation can be difficult to detect, despite the substantial “loss” of current arising from nonlinear summation. The magnitude of this “loss” appears to limit motoneuron activity, based solely on activation of iontotropic receptors, to levels that are inadequate to generate functionally meaningful muscle forces.

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