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.

Repetitive firing properties of neurons in the ventral region of nucleus tractus solitarius. In vitro studies in adult and neonatal rat

1989 ◽  
Vol 62 (6) ◽  
pp. 1213-1224 ◽  
Author(s):  
G. G. Haddad ◽  
P. A. Getting
Keyword(s):  
Steady State ◽  
Time Constant ◽  
Nucleus Tractus Solitarius ◽  
Type A ◽  
Spike Frequency ◽  
Resting Potential ◽  
Repetitive Firing ◽  
Spike Frequency Adaptation ◽  
Type B ◽  
Frequency Adaptation

1. A brain stem slice preparation and intracellular techniques were used to examine the cellular properties of neurons within the ventral and ventrolateral region of the nucleus tractus solitarius (v-NTS) in adult and neonatal (3-12 days old) rats. These neurons are believed to be involved in the control of respiratory function. 2. On the basis of their active and passive electrophysiologic properties, cells in the v-NTS of adult rats were categorized into type A and type B neurons. Type A neurons fired spontaneously with rates ranging from 0.5 to 5 spikes/s at resting potential (-59.0 +/- 6 mV, mean +/- SD). When depolarized, type A cells responded with an initial high rate of firing, which rapidly declined to a steady state level. Spike-frequency adaptation (SFA) index (defined as steady state firing divided by peak activity x 100) was 40%, with a time constant for adaptation of 100-280 ms. When depolarized from membrane potentials more negative than resting, these neurons exhibited a silent period (up to 900 ms) before any spiking was observed (delayed excitation). The delay depended on the duration and magnitude of the hyperpolarizing prepulse that preceded depolarization. The action potentials of type A cells had a shoulder on the repolarization phase, measured 2-3 ms at one-half height, and increased in duration during repetitive firing. 3. At resting potential, type B neurons fired three to five times faster than type A. Although both type A and type B neurons showed spike-frequency adaptation, type B neurons adapted at a much faster rate than type A. The time constant for adaptation was 2-14 ms in type B cells. These cells displayed no delayed excitation on depolarization from membrane potentials more negative than rest. Some type B cells exhibited postinhibitory rebound (PIR) and depolarizing afterpotentials (DAPs). Both types A and B v-NTS neurons had comparable input resistance and showed inward rectification. 4. Neonatal v-NTS cells, in contrast to adult cells, belonged to a single population of neurons. Their resting membrane potential was -58 +/- 6.3 mV (mean +/- SD). The majority of these cells (30/34) were active (5-10 spikes/s) at rest. When depolarized, they showed an immediate increase in firing rate, which gradually slowed down to reach a steady state. Spike-frequency adaptation index was 59%, with a time constant for adaptation of 300-750 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

Spike frequency adaptation studied in hypoglossal motoneurons of the rat

1995 ◽  
Vol 73 (5) ◽  
pp. 1799-1810 ◽  
Author(s):  
A. Sawczuk ◽  
R. K. Powers ◽  
M. D. Binder
Keyword(s):  
Steady State ◽  
Time Course ◽  
Firing Frequency ◽  
Spike Frequency ◽  
Membrane Properties ◽  
Repetitive Firing ◽  
Hypoglossal Nucleus ◽  
Spike Frequency Adaptation ◽  
Frequency Adaptation ◽  
Three Phases

1. We studied spike frequency adaptation of motoneuron discharge in the rat hypoglossal nucleus using a brain stem slice preparation. The characteristics of adaptation in response to long (60 s) injected current steps were qualitatively similar to those observed previously in cat hindlimb motoneurons. The discharge rate typically exhibited a rapid initial decline, characterized by a linear frequency-time relation, followed by a gradual exponential decline that continued for the duration of current injection. However, a more systematic, quantitative analysis of the data revealed that there were often three distinct phases of the adaptation rather than two. 2. The three phases of adaptation (initial, early, and late) were present in at least one 60-s trial of repetitive firing in all but a small number of motoneurons. Initial adaptation was limited to the first few spikes except in a few trials (7%) in which there was no initial adaptation. The time course of the subsequent decline in rate could be adequately described by a single-exponential function in about half of the trials (48%). In the remaining trials this subsequent decline in frequency was better described as the sum of two exponential functions: an early phase, lasting < 2 s, and a late phase, which lasted for the duration of the discharge period. 3. The magnitude of initial adaptation was correlated with the initial firing frequency (i.e., the reciprocal of the 1st interspike interval). The magnitudes of the early and late phases of adaptation were correlated with the firing frequency reached at the end of initial adaptation. Neither the magnitudes nor the time courses of the three phases were correlated with other membrane properties such as input resistance, rheobase, or repetitive firing threshold. 4. The slope of the frequency-current (f-I) curve was steeper in the initial phase (first 2-5 spikes) than in either the early (< 2 s) or late (> 2 s) phases of adaptation as previously reported by other investigators. In the absence of early adaptation, a steady state for the f-I slope was reached by 0.7-1 s, the time typically reported in studies of repetitive discharge. However, when early adaptation was present (50% of the trials), a steady-state value for the f-I slope was not reached until the cell had discharged for > 1 s. 5. To characterize the time course of firing rate recovery from the adaptive processes, the current was turned off for periods of < or = 10 s during the course of a 60-s trial.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

scholarly journals The Effects of Spike Frequency Adaptation and Negative Feedback on the Synchronization of Neural Oscillators

2001 ◽  
Vol 13 (6) ◽  
pp. 1285-1310 ◽  
Author(s):  
Bard Ermentrout ◽  
Matthew Pascal ◽  
Boris Gutkin
Keyword(s):  
Cortical Neurons ◽  
Potassium Current ◽  
Spike Frequency ◽  
Repetitive Firing ◽  
Spike Frequency Adaptation ◽  
Calcium Dependent ◽  
M Current ◽  
Frequency Adaptation ◽  
Voltage Dependent ◽  
Standard Models

There are several different biophysical mechanisms for spike frequency adaptation observed in recordings from cortical neurons. The two most commonly used in modeling studies are a calcium-dependent potassium current Iahp and a slow voltage-dependent potassium current, Im. We show that both of these have strong effects on the synchronization properties of excitatorily coupled neurons. Furthermore, we show that the reasons for these effects are different. We show through an analysis of some standard models, that the M-current adaptation alters the mechanism for repetitive firing, while the after hyperpolarization adaptation works via shunting the incoming synapses. This latter mechanism applies with a network that has recurrent inhibition. The shunting behavior is captured in a simple two-variable reduced model that arises near certain types of bifurcations. A one-dimensional map is derived from the simplified model.

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.

Contribution of Persistent Sodium Currents to Spike-Frequency Adaptation in Rat Hypoglossal Motoneurons

2005 ◽  
Vol 93 (2) ◽  
pp. 1035-1041 ◽  
Author(s):  
Jinsong Zeng ◽  
Randall K. Powers ◽  
Gregory Newkirk ◽  
Marc Yonkers ◽  
Marc D. Binder
Keyword(s):  
Time Course ◽  
Spike Frequency ◽  
Constant Current ◽  
Repetitive Firing ◽  
Bathing Solution ◽  
Appreciable Effect ◽  
Spike Frequency Adaptation ◽  
Hypoglossal Motoneurons ◽  
Frequency Adaptation ◽  
Later Phase

In response to constant current inputs, the firing rates of motoneurons typically show a continuous decline over time. The biophysical mechanisms underlying this process, called spike-frequency adaptation, are not well understood. Spike-frequency adaptation normally exhibits a rapid initial phase, followed by a slow, later phase that continues throughout the duration of firing. One possible mechanism mediating the later phase might be a reduction in the persistent sodium current ( INaP) that has been shown to diminish the capacity of cortical pyramidal neurons and spinal motoneurons to sustain repetitive firing. In this study, we used the anticonvulsant phenytoin to reduce the INaP of juvenile rat hypoglossal motoneurons recorded in brain stem slices, and we examined the consequences of a reduction in INaP on the magnitude and time course of spike-frequency adaptation. Adding phenytoin to the bathing solution (≥50 μM) generally produced a marked reduction in the persistent inward currents (PICs) recorded at the soma in response to slow, voltage-clamp triangular ramp commands (−70 to 0 mV and back). However, the same concentrations of phenytoin appeared to have no significant effect on spike-frequency adaptation even though the phenytoin often augmented the reduction in action potential amplitude that occurs during repetitive firing. The surprising finding that the reduction of a source of sustained inward current had no appreciable effect on the pattern of spike generation suggests that several types of membrane channels must act cooperatively to insure that these motoneurons can generate the sustained repetitive firing required for long-lasting motor behaviors.

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