scholarly journals Opening of KATP Channel Regulates Tonic Currents From Pyramidal Neurons in Rat Brain

2017 ◽  
Vol 44 (6) ◽  
pp. 718-725
Author(s):  
Zhongxia Li ◽  
Jiangping Wang ◽  
Huimin Yu ◽  
Kewen Jiang
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Cortical Layer ◽  
Gaba A ◽  
Gaba Inhibition ◽  
Ambient Gaba ◽  
Neuronal Functions ◽  
Tonic Current ◽  
The Impact

AbstractBackground: ATP-sensitive K+ (KATP) channels couple metabolic state to cellular excitability. Activation of neuronal and astrocytic mitochondrial KATP (mitoKATP) channels regulates a variety of neuronal functions. However, less is known about the impact of mitoKATP on tonic γ-aminobutyric acid (GABA) inhibition. Tonic GABA inhibition is mediated by the binding of ambient GABA on extrasynaptic GABA A-type receptors (GABAARs) and is involved in regulating neuronal excitability. Methods: We determined the impact of activation of KATP channels with diazoxide (DIZ) on tonic inhibition and recorded tonic current from rat cortical layer 5 pyramidal cells by patch-clamp recordings. Results: We found that neonatal tonic current increased with an increase in GABA concentration, which was partially mediated by the GABA A-type receptor (GABAAR) α5, and likely the δ subunits. Activation of KATP channels resulted in decreased tonic current in newborns, but there was increased tonic current during the second postnatal week. Conclusions: These findings suggest that activation of KATP channels with DIZ regulates GABAergic transmission in neocortical pyramidal cells during development.

scholarly journals Potassium channels contribute to activity-dependent scaling of dendritic inhibition

2017 ◽  
Author(s):  
Jeremy T. Chang ◽  
Michael J. Higley
Keyword(s):  
Potassium Channels ◽  
Neuronal Activity ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Gabaergic Inhibition ◽  
Voltage Gated ◽  
The Impact ◽  
Activity Dependent

AbstractGABAergic inhibition plays a critical role in the regulation of neuronal activity. In the neocortex, inhibitory interneurons that target the dendrites of pyramidal cells influence both electrical and biochemical postsynaptic signaling. Voltage-gated ion channels strongly shape dendritic excitability and the integration of excitatory inputs, but their contribution to GABAergic signaling is less well understood. By combining 2-photon calcium imaging and focal GABA uncaging, we show that voltage-gated potassium channels normally suppress the GABAergic inhibition of calcium signals evoked by back-propagating action potentials in dendritic spines and shafts of cortical pyramidal neurons. Moreover, the voltage-dependent inactivation of these channels leads to enhancement of dendritic calcium inhibition following somatic spiking. Computational modeling reveals that the enhancement of calcium inhibition involves an increase in action potential depolarization coupled with the nonlinear relationship between membrane voltage and calcium channel activation. Overall, our findings highlight the interaction between intrinsic and synaptic properties and reveal a novel mechanism for the activity-dependent scaling of GABAergic inhibition.Significance StatementGABAergic inhibition potently regulates neuronal activity in the neocortex. How such inhibition interacts with the intrinsic electrophysiological properties of single neurons is not well-understood. Here we investigate the ability of voltage-gated potassium channels to regulate the impact of GABAergic inhibition in the dendrites of neocortical pyramidal neurons. Our results show that potassium channels normally reduce inhibition directed towards pyramidal neuron dendrites. However, these channels are inactivated by strong neuronal activity, leading to an enhancement of GABAergic potency and limiting the corresponding influx of dendritic calcium. Our findings illustrate a previously unappreciated relationship between neuronal excitability and GABAergic inhibition.

Differential Impact of Miniature Synaptic Potentials on the Soma and Dendrites of Pyramidal Neurons In Vivo

1997 ◽  
Vol 78 (3) ◽  
pp. 1735-1739 ◽  
Author(s):  
Denis Paré ◽  
Elen Lebel ◽  
Eric J. Lang
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Differential Impact ◽  
Synaptic Potentials ◽  
Ampa Antagonists ◽  
Intact Brain ◽  
The Impact

Paré, Denis, Elen LeBel, and Eric J. Lang. Differential impact of miniature synaptic potentials on the somata and dendrites of pyramidal neurons in vivo. J. Neurophysiol. 78: 1735–1739, 1997. We studied the impact of transmitter release resistant to tetrodotoxin (TTX) in morphologically identified neocortical pyramidal neurons recorded intracellularly in barbiturate-anesthetized cats. It was observed that TTX-resistant release occurs in pyramidal neurons in vivo and at much higher frequencies than was previously reported in vitro. Further, in agreement with previous findings indicating that GABAergic and glutamatergic synapses are differentially distributed in the somata and dendrites of pyramidal cells, we found that most miniature synaptic potentials were sensitive to γ-aminobutyric acid-A (GABAA) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists in presumed somatic and dendritic impalements, respectively. Pharmacological blockage of spontaneous synaptic events produced large increases in input resistance that were more important in dendritic (≈50%) than somatic (≈10%) impalements. These findings imply that in the intact brain, pyramidal neurons are submitted to an intense spike-independent synaptic bombardment that decreases the space constant of the cells. These results should be taken into account when extrapolating in vitro findings to intact brains.

Neuromodulation by a Cytokine: Interferon-β Differentially Augments Neocortical Neuronal Activity and Excitability

2005 ◽  
Vol 93 (2) ◽  
pp. 843-852 ◽  
Author(s):  
Gergana Hadjilambreva ◽  
Eilhard Mix ◽  
Arndt Rolfs ◽  
Jana Müller ◽  
Ulf Strauss
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Membrane Resistance ◽  
Interferon Β ◽  
Action Potential Firing ◽  
Somatosensory Neurons ◽  
Potential Firing ◽  
Intracellular Process ◽  
Neuronal Functions

The immunomodulatory cytokine interferon-β (IFN-β) is used in the treatment of autoimmune diseases such as multiple sclerosis. However, the effect of IFN-β on neuronal functions is currently unknown. Intracellular recordings were conducted on somatosensory neurons of neocortical layers 2/3 and 5 exposed to IFN-β. The excitability of neurons was increased by IFN-β (10–10,000 U/ml) in two kinetically distinct, putatively independent manners. First IFN-β reversibly influenced the subthreshold membrane response by raising the membrane resistance RM 2.5-fold and the membrane time constant τ 1.7-fold dose-dependently. The effect required permanent exposure to IFN-β and was reduced in magnitude if the extracellular K+ was lowered. However, the membrane response to IFN-β in the subthreshold range was prevented by ZD7288 (a specific blocker of Ih) but not by Ni2+, carbachol, or bicuculline, pointing to a dependence on an intact Ih. Second, IFN-β enhanced the rate of action potential firing. This effect was observed to develop for >1 h when the cell was exposed to IFN-β for 5 min or >5 min and showed no reversibility (≤210 min). Current-discharge ( F-I) curves revealed a shift (prevented by bicuculline) as well as an increase in slope (prevented by carbachol and Ni2+). Layer specificity was not observed with any of the described effects. In conclusion, IFN-β influences the neuronal excitability in neocortical pyramidal neurons in vitro, especially under conditions of slightly increased extracellular K+. Our blocker experiments indicate that changes in various ionic conductances with different voltage dependencies cause different IFN-β influences on sub- and suprathreshold behavior, suggesting a more general intracellular process induced by IFN-β.

scholarly journals A Multi-Scale Computational Model of the effects of TMS on Motor Cortex

2016 ◽  
Author(s):  
Hyeon Seo ◽  
Natalie Schaworonkow ◽  
Sung Chan Jun ◽  
Jochen Triesch
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Computational Model ◽  
Electric Fields ◽  
Action Potentials ◽  
Magnetic Stimulation ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Cortical Layer ◽  
Multi Scale

AbstractThe detailed biophysical mechanisms through which transcranial magnetic stimulation (TMS) activates cortical circuits are still not fully understood. Here we present a multi-scale computational model to describe and explain the activation of different cell types in motor cortex due to transcranial magnetic stimulation. Our model determines precise electric fields based on an individual head model derived from magnetic resonance imaging and calculates how these electric fields activate morphologically detailed models of different neuron types. We predict detailed neural activation patterns for different coil orientations consistent with experimental findings. Beyond this, our model allows us to predict activation thresholds for individual neurons and precise initiation sites of individual action potentials on the neurons’ complex morphologies. Specifically, our model predicts that cortical layer 3 pyramidal neurons are generally easier to stimulate than layer 5 pyramidal neurons, thereby explaining the lower stimulation thresholds observed for I-waves compared to D-waves. It also predicts differences in the regions of activated cortical layer 5 and layer 3 pyramidal cells depending on coil orientation. Finally, it predicts that under standard stimulation conditions, action potentials are mostly generated at the axon initial segment of corctial pyramidal cells, with a much less important activation site being the part of a layer 5 pyramidal cell axon where it crosses the boundary between grey matter and white matter. In conclusion, our computational model offers a detailed account of the mechanisms through which TMS activates different cortical cell types, paving the way for more targeted application of TMS based on individual brain morphology in clinical and basic research settings.

scholarly journals Somatic and dendritic GABAB receptors regulate neuronal excitability via different mechanisms

2012 ◽  
Vol 108 (10) ◽  
pp. 2810-2818 ◽  
Author(s):  
Jean-Didier Breton ◽  
Greg J. Stuart
Keyword(s):  
Potassium Channels ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Barrel Cortex ◽  
Receptor Activation ◽  
Gabab Receptors ◽  
Membrane Properties ◽  
Dendritic Excitability ◽  
The Impact ◽  
Neuronal Output

GABAB receptors play a key role in regulating neuronal excitability in the brain. Whereas the impact of somatic GABAB receptors on neuronal excitability has been studied in some detail, much less is known about the role of dendritic GABAB receptors. Here, we investigate the impact of GABAB receptor activation on the somato-dendritic excitability of layer 5 pyramidal neurons in the rat barrel cortex. Activation of GABAB receptors led to hyperpolarization and a decrease in membrane resistance that was greatest at somatic and proximal dendritic locations. These effects were occluded by low concentrations of barium (100 μM), suggesting that they are mediated by potassium channels. In contrast, activation of dendritic GABAB receptors decreased the width of backpropagating action potential (APs) and abolished dendritic calcium electrogenesis, indicating that dendritic GABAB receptors regulate excitability, primarily via inhibition of voltage-dependent calcium channels. These distinct actions of somatic and dendritic GABAB receptors regulated neuronal output in different ways. Activation of somatic GABAB receptors led to a reduction in neuronal output, primarily by increasing the AP rheobase, whereas activation of dendritic GABAB receptors blocked burst firing, decreasing AP output in the absence of a significant change in somatic membrane properties. Taken together, our results show that GABAB receptors regulate somatic and dendritic excitability of cortical pyramidal neurons via different cellular mechanisms. Somatic GABAB receptors activate potassium channels, leading primarily to a subtractive or shunting form of inhibition, whereas dendritic GABAB receptors inhibit dendritic calcium electrogenesis, leading to a reduction in bursting firing.

scholarly journals Impact of inhibitory constraint of interneurons on neuronal excitability

2013 ◽  
Vol 110 (11) ◽  
pp. 2520-2535 ◽  
Author(s):  
Vallent Lee ◽  
Jamie Maguire
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Molecular Layer ◽  
Critical Role ◽  
Tonic Inhibition ◽  
Stratum Radiatum ◽  
Gabaergic Inhibition ◽  
Seizure Susceptibility ◽  
Ca1 Pyramidal Neurons ◽  
The Impact

Tonic inhibition is thought to dampen the excitability of principal neurons; however, little is known about the role of tonic GABAergic inhibition in interneurons and the impact on principal neuron excitability. In many brain regions, tonic GABAergic inhibition is mediated by extrasynaptic, δ-subunit-containing GABAA receptors (GABAARs). In the present study we demonstrate the importance of GABAAR δ-subunit-mediated tonic inhibition in interneurons. Selective elimination of the GABAAR δ-subunit from interneurons was achieved by crossing a novel floxed Gabrd mouse model with GAD65-Cre mice ( Gabrd/Gad mice). Deficits in GABAAR δ-subunit expression in GAD65-positive neurons result in a decrease in tonic GABAergic inhibition and increased excitability of both molecular layer (ML) and stratum radiatum (SR) interneurons. Disinhibition of interneurons results in robust alterations in the neuronal excitability of principal neurons and decreased seizure susceptibility. Gabrd/Gad mice have enhanced tonic and phasic GABAergic inhibition in both CA1 pyramidal neurons and dentate gyrus granule cells (DGGCs). Consistent with alterations in hippocampal excitability, CA1 pyramidal neurons and DGGCs from Gabrd/Gad mice exhibit a shift in the input-output relationship toward decreased excitability compared with those from Cre−/− littermates. Furthermore, seizure susceptibility, in response to 20 mg/kg kainic acid, is significantly decreased in Gabrd/Gad mice compared with Cre−/− controls. These data demonstrate a critical role for GABAAR δ-subunit-mediated tonic GABAergic inhibition of interneurons on principal neuronal excitability and seizure susceptibility.

scholarly journals Burst control: Synaptic conditions for burst generation in cortical layer 5 pyramidal neurons

2021 ◽  
Vol 17 (11) ◽  
pp. e1009558
Author(s):  
Eilam Goldenberg Leleo ◽  
Idan Segev
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Excitatory Input ◽  
Cortical Layer ◽  
Coincidence Detection ◽  
High Frequencies ◽  
Synaptic Inputs ◽  
Apical Tuft ◽  
Output Spike ◽  
Spike Bursts

The output of neocortical layer 5 pyramidal cells (L5PCs) is expressed by a train of single spikes with intermittent bursts of multiple spikes at high frequencies. The bursts are the result of nonlinear dendritic properties, including Na+, Ca2+, and NMDA spikes, that interact with the ~10,000 synapses impinging on the neuron’s dendrites. Output spike bursts are thought to implement key dendritic computations, such as coincidence detection of bottom-up inputs (arriving mostly at the basal tree) and top-down inputs (arriving mostly at the apical tree). In this study we used a detailed nonlinear model of L5PC receiving excitatory and inhibitory synaptic inputs to explore the conditions for generating bursts and for modulating their properties. We established the excitatory input conditions on the basal versus the apical tree that favor burst and show that there are two distinct types of bursts. Bursts consisting of 3 or more spikes firing at < 200 Hz, which are generated by stronger excitatory input to the basal versus the apical tree, and bursts of ~2-spikes at ~250 Hz, generated by prominent apical tuft excitation. Localized and well-timed dendritic inhibition on the apical tree differentially modulates Na+, Ca2+, and NMDA spikes and, consequently, finely controls the burst output. Finally, we explored the implications of different burst classes and respective dendritic inhibition for regulating synaptic plasticity.

scholarly journals Rapid Temporal Modulation of Synchrony by Competition in Cortical Interneuron Networks

2004 ◽  
Vol 16 (2) ◽  
pp. 251-275 ◽  
Author(s):  
P.H.E. Tiesinga ◽  
T. J. Sejnowski
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Background Activity ◽  
Pyramidal Cells ◽  
Spike Timing ◽  
Network Activity ◽  
Local Networks ◽  
Rapid Changes ◽  
Asynchronous State ◽  
The Impact

The synchrony of neurons in extrastriate visual cortex is modulated by selective attention even when there are only small changes in firing rate (Fries, Reynolds, Rorie, & Desimone, 2001). We used Hodgkin-Huxley type models of cortical neurons to investigate the mechanism by which the degree of synchrony can be modulated independently of changes in firing rates. The synchrony of local networks of model cortical interneurons interacting through GABAA synapses was modulated on a fast timescale by selectively activating a fraction of the interneurons. The activated interneurons became rapidly synchronized and suppressed the activity of the other neurons in the network but only if the network was in a restricted range of balanced synaptic background activity. During stronger background activity, the network did not synchronize, and for weaker background activity, the network synchronized but did not return to an asynchronous state after synchronizing. The inhibitory output of the network blocked the activity of pyramidal neurons during asynchronous network activity, and during synchronous network activity, it enhanced the impact of the stimulus-related activity of pyramidal cells on receiving cortical areas (Salinas & Sejnowski, 2001). Synchrony by competition provides a mechanism for controlling synchrony with minor alterations in rate, which could be useful for information processing. Because traditional methods such as cross-correlation and the spike field coherence require several hundred milliseconds of recordings and cannot measure rapid changes in the degree of synchrony, we introduced a new method to detect rapid changes in the degree of coincidence and precision of spike timing.

Altered dendritic complexity affects firing properties of cortical layer 2/3 pyramidal neurons in mice lacking the 5-HT3A receptor

2012 ◽  
Vol 108 (5) ◽  
pp. 1521-1528 ◽  
Author(s):  
Luuk van der Velden ◽  
Johannes A. van Hooft ◽  
Pascal Chameau
Keyword(s):  
Firing Pattern ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Dendritic Morphology ◽  
Neuronal Firing ◽  
Specific Class ◽  
Postnatal Maturation ◽  
Layer 2 ◽  
The Impact ◽  
Dendritic Complexity

We have previously shown that the serotonergic input on Cajal-Retzius cells, mediated by 5-HT3 receptors, plays an important role in the early postnatal maturation of the apical dendritic trees of layer 2/3 pyramidal neurons. We reported that knockout mice lacking the 5-HT3A receptor showed exuberant apical dendrites of these cortical pyramidal neurons. Because model studies have shown the role of dendritic morphology on neuronal firing pattern, we used the 5-HT3A knockout mouse to explore the impact of dendritic hypercomplexity on the electrophysiological properties of this specific class of neurons. Our experimental results show that hypercomplexity of the apical dendritic tuft of layer 2/3 pyramidal neurons affects neuronal excitability by reducing the amount of spike frequency adaptation. This difference in firing pattern, related to a higher dendritic complexity, was accompanied by an altered development of the afterhyperpolarization slope with successive action potentials. Our abstract and realistic neuronal models, which allowed manipulation of the dendritic complexity, showed similar effects on neuronal excitability and confirmed the impact of apical dendritic complexity. Alterations of dendritic complexity, as observed in several pathological conditions such as neurodegenerative diseases or neurodevelopmental disorders, may thus not only affect the input to layer 2/3 pyramidal neurons but also shape their firing pattern and consequently alter the information processing in the cortex.

Control of layer 5 pyramidal cell spiking by oscillatory inhibition in the distal apical dendrites: a computational modeling study

2013 ◽  
Vol 109 (11) ◽  
pp. 2739-2756 ◽  
Author(s):  
Xiumin Li ◽  
Kenji Morita ◽  
Hugh P. C. Robinson ◽  
Michael Small
Keyword(s):  
Pyramidal Cell ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Recurrent Inhibition ◽  
Aspartate Receptor ◽  
Coupled Cells ◽  
Single Spike ◽  
Cell Firing ◽  
The Impact ◽  
Apical Dendrites

The distal apical dendrites of layer 5 pyramidal neurons receive cortico-cortical and thalamocortical top-down and feedback inputs, as well as local recurrent inputs. A prominent source of recurrent inhibition in the neocortical circuit is somatostatin-positive Martinotti cells, which preferentially target distal apical dendrites of pyramidal cells. These electrically coupled cells can fire synchronously at various frequencies, including over a relatively slow range (5∼30 Hz), thereby imposing oscillatory inhibition on the pyramidal apical tuft dendrites. We examined how such distal oscillatory inhibition influences the firing of a biophysically detailed layer 5 pyramidal neuron model, which reproduced the spatiotemporal properties of sodium, calcium, and N-methyl-d-aspartate receptor spikes found experimentally. We found that oscillatory synchronization strongly influences the impact of distal inhibition on the pyramidal cell firing. Whereas asynchronous inhibition largely cancels out the facilitatory effects of distal excitatory inputs, inhibition oscillating synchronously at around 10∼20 Hz allows distal excitation to drive axosomatic firing, as if distal inhibition were absent. Underlying this is a switch from relatively infrequent burst firing to single spike firing at every period of the inhibitory oscillation. This phenomenon depends on hyperpolarization-activated cation current-dependent membrane potential resonance in the dendrite, but also, in a novel manner, on a cooperative amplification of this resonance by N-methyl-d-aspartate-receptor-driven dendritic action potentials. Our results point to a surprising dependence of the effect of recurrent inhibition by Martinotti cells on their oscillatory synchronization, which may control not only the local circuit activity, but also how it is transmitted to and decoded by downstream circuits.

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