scholarly journals Selective attenuation of Ether-a-go-go related K+ currents by endogenous acetylcholine reduces spike-frequency adaptation and network correlation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Edward D Cui ◽  
Ben W Strowbridge
Keyword(s):  
Late Phase ◽  
Pyramidal Cells ◽  
Spike Frequency ◽  
Spike Frequency Adaptation ◽  
Firing Rates ◽  
Frequency Adaptation ◽  
Rat Neocortex ◽  
Persistent Firing ◽  
K Current

Most neurons do not simply convert inputs into firing rates. Instead, moment-to-moment firing rates reflect interactions between synaptic inputs and intrinsic currents. Few studies investigated how intrinsic currents function together to modulate output discharges and which of the currents attenuated by synthetic cholinergic ligands are actually modulated by endogenous acetylcholine (ACh). In this study we optogenetically stimulated cholinergic fibers in rat neocortex and find that ACh enhances excitability by reducing Ether-à-go-go Related Gene (ERG) K+ current. We find ERG mediates the late phase of spike-frequency adaptation in pyramidal cells and is recruited later than both SK and M currents. Attenuation of ERG during coincident depolarization and ACh release leads to reduced late phase spike-frequency adaptation and persistent firing. In neuronal ensembles, attenuating ERG enhanced signal-to-noise ratios and reduced signal correlation, suggesting that these two hallmarks of cholinergic function in vivo may result from modulation of intrinsic properties.

Electrophysiological Classes of Cat Primary Visual Cortical Neurons In Vivo as Revealed by Quantitative Analyses

2003 ◽  
Vol 89 (3) ◽  
pp. 1541-1566 ◽  
Author(s):  
Lionel G. Nowak ◽  
Rony Azouz ◽  
Maria V. Sanchez-Vives ◽  
Charles M. Gray ◽  
David A. McCormick
Keyword(s):  
Short Duration ◽  
Cortical Neurons ◽  
Action Potentials ◽  
Low Frequency ◽  
Pyramidal Cells ◽  
Spike Frequency ◽  
Spike Frequency Adaptation ◽  
Frequency Adaptation ◽  
Layer 4

To facilitate the characterization of cortical neuronal function, the responses of cells in cat area 17 to intracellular injection of current pulses were quantitatively analyzed. A variety of response variables were used to separate the cells into subtypes using cluster analysis. Four main classes of neurons could be clearly distinguished: regular spiking (RS), fast spiking (FS), intrinsic bursting (IB), and chattering (CH). Each of these contained significant subclasses. RS neurons were characterized by trains of action potentials that exhibited spike frequency adaptation. Morphologically, these cells were spiny stellate cells in layer 4 and pyramidal cells in layers 2, 3, 5, and 6. FS neurons had short-duration action potentials (<0.5 ms at half height), little or no spike frequency adaptation, and a steep relationship between injected current intensity and spike discharge frequency. Morphologically, these cells were sparsely spiny or aspiny nonpyramidal cells. IB neurons typically generated a low frequency (<425 Hz) burst of spikes at the beginning of a depolarizing current pulse followed by a tonic train of action potentials for the remainder of the pulse. These cells were observed in all cortical layers, but were most abundant in layer 5. Finally, CH neurons generated repetitive, high-frequency (350–700 Hz) bursts of short-duration (<0.55 ms) action potentials. Morphologically, these cells were layer 2–4 (mainly layer 3) pyramidal or spiny stellate neurons. These results indicate that firing properties do not form a continuum and that cortical neurons are members of distinct electrophysiological classes and subclasses.

scholarly journals Slow Spike Frequency Adaptation in Neurons of the Rat Subthalamic Nucleus

2009 ◽  
Vol 102 (6) ◽  
pp. 3689-3697 ◽  
Author(s):  
David Barraza ◽  
Hitoshi Kita ◽  
Charles J. Wilson
Keyword(s):  
Firing Rate ◽  
Subthalamic Nucleus ◽  
Similar Rate ◽  
Excitatory Input ◽  
Spike Frequency ◽  
Spike Frequency Adaptation ◽  
Frequency Adaptation ◽  
Long Duration ◽  
Subthalamic Neurons

Neurons of the subthalamic nucleus (STN) are very sensitive to applied currents, firing at 10–20/s during spontaneous activity, but increasing to peak firing rates of 200/s with applied currents <0.5 nA. They receive a powerful tonic excitatory input from neurons in the cerebral cortex, yet in vivo maintain an irregular firing rate only slightly higher than the autonomous firing rate seen in slices. Spike frequency adaptation acts to normalize background firing rate by removing slow trends in firing due to changes in average input. Subthalamic neurons have been previously described as showing little spike frequency adaptation, but this was based on tests using brief stimuli. We applied long-duration depolarizing current steps to STN neurons in slices and observed a very strong spike frequency adaptation with a time constant of 20 s and that recovered at a similar rate. This adaptation could return firing to near-baseline levels during prolonged current pulses that transiently drove the cells at high rates. The current responsible for adaptation was studied in voltage clamp during and after high-frequency driving of the cell and was determined to be a slowly accumulating K+ current. This current was independent of calcium or sodium entry and could be induced with long-duration voltage steps after blockade of action potentials. In addition to the adaptation current, driven firing produced slow inactivation of the persistent Na+ current, which also contributed to the reduced excitability of STN cells during and after driven firing.

scholarly journals Spike Frequency Adaptation Affects the Synchronization Properties of Networks of Cortical Oscillators

1998 ◽  
Vol 10 (4) ◽  
pp. 837-854 ◽  
Author(s):  
Sharon M. Crook ◽  
G. Bard Ermentrout ◽  
James M. Bower
Keyword(s):  
Pyramidal Cells ◽  
Rhythmic Activity ◽  
Spike Frequency ◽  
Spike Frequency Adaptation ◽  
Frequency Range ◽  
Cortical Dynamics ◽  
Gamma Frequency ◽  
Frequency Adaptation ◽  
Theta Frequency ◽  
Synchronous Behavior

Oscillations in many regions of the cortex have common temporal characteristics with dominant frequencies centered around the 40 Hz (gamma) frequency range and the 5–10 Hz (theta) frequency range. Experimental results also reveal spatially synchronous oscillations, which are stimulus dependent (Gray&Singer, 1987;Gray, König, Engel, & Singer, 1989; Engel, König, Kreiter, Schillen, & Singer, 1992). This rhythmic activity suggests that the coherence of neural populations is a crucial feature of cortical dynamics (Gray, 1994). Using both simulations and a theoretical coupled oscillator approach, we demonstrate that the spike frequency adaptation seen in many pyramidal cells plays a subtle but important role in the dynamics of cortical networks. Without adaptation, excitatory connections among model pyramidal cells are desynchronizing. However, the slow processes associated with adaptation encourage stable synchronous behavior.

Dopamine modulates the slow Ca(2+)-activated K+ current IAHP via cyclic AMP-dependent protein kinase in hippocampal neurons

1995 ◽  
Vol 74 (6) ◽  
pp. 2749-2753 ◽  
Author(s):  
P. Pedarzani ◽  
J. F. Storm
Keyword(s):  
Protein Kinase ◽  
Voltage Clamp ◽  
Cell Voltage ◽  
Spike Frequency ◽  
Receptor Type ◽  
Spike Frequency Adaptation ◽  
Current Clamp ◽  
Whole Cell ◽  
Frequency Adaptation ◽  
K Current

1. The effects of dopamine on the slow Ca(2+)-dependent K+ current (IAHP; AHP, afterhyperpolarization) and spike frequency adaptation were studied by whole cell voltage-clamp and sharp microelectrode current-clamp recordings in rat CA1 pyramidal neurons in rat hippocampal slices. 2. Dopamine suppressed IAHP in a dose-dependent manner, under whole cell voltage-clamp conditions. Similarly, under current-clamp conditions, dopamine inhibited spike frequency adaptation and suppressed the slow afterhyperpolarization. 3. The effect of dopamine on IAHP was mimicked by a D1 receptor agonist and blocked by dopamine receptor antagonists only in a minority of the cells. 4. Dopamine suppressed IAHP after blocking or desensitizing the beta-adrenergic receptors and, hence, did not act by cross-reacting with this receptor type. 5. The effects of dopamine on IAHP and spike frequency adaptation were suppressed by blocking the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent kinase (PKA) with Rp-cAMPS and, hence, are probably mediated by the activation of this kinase. 6. We conclude that dopamine increases hippocampal neuron excitability, like other monoamine neurotransmitters, by suppressing IAHP and spike frequency adaptation, via cAMP and protein kinase A. The receptor type mediating this effect of dopamine remains to be defined.

Relationship between repetitive firing and afterhyperpolarizations in human neocortical neurons

1992 ◽  
Vol 67 (2) ◽  
pp. 350-363 ◽  
Author(s):  
N. M. Lorenzon ◽  
R. C. Foehring
Keyword(s):  
Interspike Interval ◽  
Reversal Potential ◽  
Spike Frequency ◽  
Resting Potential ◽  
Repetitive Firing ◽  
Spike Frequency Adaptation ◽  
Neocortical Neurons ◽  
Frequency Adaptation ◽  
K Current ◽  
Pharmacological Manipulations

1. Human neocortical neurons fire repetitively in response to long depolarizing current injections. The slope of the relationship between average firing frequency and injected current (f-I slope) was linear or bilinear in these cells. The mean steady-state f-I slope (average of the last 500 ms of a 1-s firing episode) was 57.8 Hz/nA. The instantaneous firing rate decreased with time during a 1-s constant-current injection (spike frequency adaptation). Also, human neurons exhibited habituation in response to a 1-s current stimulus repeated every 2 s. 2. Afterhyperpolarizations (AHPs) reflect the active ionic conductances after action potentials. We studied AHPs with the use of intracellular recordings and pharmacological manipulations in the in vitro slice preparation to 1) gain insight into the ionic mechanisms underlying the AHPs and 2) elucidate the role that the underlying currents play in the functional behavior of human cortical neurons. 3. We have classified three AHPs in human neocortical neurons on the basis of their time courses: fast, medium, and slow. The amplitude of the AHPs was dependent on stimulus intensity and duration, number and frequency of spikes, and membrane potential. 4. The fast AHP had a reversal potential of -65 mV and was eliminated in extracellular Co2+, tetraethylammonium (TEA) or 4-aminopyridine, and intracellular TEA or CsCl. These manipulations also caused an increase in spike width. 5. The medium AHP had a reversal potential of -90 to -93 mV (22-24 mV hyperpolarized from mean resting potential). This AHP was reduced by Co2+, apamin, tubocurare, muscarine, norepinephrine (NE), and serotonin (5-HT). Pharmacological manipulations suggest that the medium AHP is produced in part by 1) a Ca-dependent K+ current and 2) a time-dependent anomalous rectifier (IH). 6. The slow AHP reversed at -83 to -87 mV (14-18 mV hyperpolarized from mean resting potential). This AHP was diminished by Co2+, muscarine, NE, and 5-HT. The pharmacology of the slow AHP suggests that a Ca-dependent K+ current with slow kinetics contributes to this AHP. 7. The currents involved in the fast AHP are important in spike repolarization, control of interspike interval during repetitive firing, and prevention of burst firing. Currents underlying the medium and slow AHPs influence the interspike interval during repetitive firing and produce spike frequency adaptation and habituation.

scholarly journals Spike Frequency Adaptation and Neocortical Rhythms

2002 ◽  
Vol 88 (2) ◽  
pp. 761-770 ◽  
Author(s):  
Galit Fuhrmann ◽  
Henry Markram ◽  
Misha Tsodyks
Keyword(s):  
Firing Rate ◽  
Pyramidal Neurons ◽  
Spike Frequency ◽  
Spike Frequency Adaptation ◽  
Patch Clamp Technique ◽  
Response Characteristics ◽  
Frequency Adaptation ◽  
Whole Cell Patch Clamp ◽  
The Mean

Spike-frequency adaptation in neocortical pyramidal neurons was examined using the whole cell patch-clamp technique and a phenomenological model of neuronal activity. Noisy current was injected to reproduce the irregular firing typically observed under in vivo conditions. The response was quantified by computing the poststimulus histogram (PSTH). To simulate the spiking activity of a pyramidal neuron, we considered an integrate-and-fire model to which an adaptation current was added. A simplified model for the mean firing rate of an adapting neuron under noisy conditions is also presented. The mean firing rate model provides a good fit to both experimental and simulation PSTHs and may therefore be used to study the response characteristics of adapting neurons to various input currents. The models enable identification of the relevant parameters of adaptation that determine the shape of the PSTH and allow the computation of the response to any change in injected current. The results suggest that spike frequency adaptation determines a preferred frequency of stimulation for which the phase delay of a neuron's activity relative to an oscillatory input is zero. Simulations show that the preferred frequency of single neurons dictates the frequency of emergent population rhythms in large networks of adapting neurons. Adaptation could therefore be one of the crucial factors in setting the frequency of population rhythms in the neocortex.

scholarly journals Reversal of the late phase of spike frequency adaptation in cat spinal motoneurons during fictive locomotion

2011 ◽  
Vol 105 (3) ◽  
pp. 1045-1050 ◽  
Author(s):  
Robert M. Brownstone ◽  
Sherry Krawitz ◽  
Larry M. Jordan
Keyword(s):  
Late Phase ◽  
Force Production ◽  
Spike Frequency ◽  
Fictive Locomotion ◽  
Spike Frequency Adaptation ◽  
Spinal Motoneurons ◽  
Frequency Adaptation ◽  
State Dependent ◽  
Adult Cat ◽  
Late Adaptation

In spinal motoneurons, late spike frequency adaptation (SFA) is defined as the slowing of the firing rate over tens of seconds and can be seen during sustained or intermittent current injection. Although the function of late SFA is not known, it may result in a decrease in force production over time, or muscle fatigue. Because locomotion can persist for long periods of time without fatigue, late SFA was studied using intracellular recordings from adult cat motoneurons during fictive locomotion. Of eight lumbar motoneurons studied, all showed late adaptation during control conditions, but none demonstrated late adaptation during locomotor activity. The most consistent properties that correlated with the presence or absence of late SFA were those related to availability of fast, inactivating sodium channels, particularly action potential rate of rise. Evidence of the reversal of late SFA during locomotion was present for several minutes following locomotor trials, consistent with the suggestion that SFA is modulated through slow metabotropic pathways. The abolition of late adaptation in spinal motoneurons during fictive locomotion is an example of a state-dependent change in the “intrinsic” properties of mammalian motoneurons. This change contributes to increased excitability of motoneurons during locomotion and results in robust firing during sustained locomotion.

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