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.

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 Contribution of Outward Currents to Spike-Frequency Adaptation in Hypoglossal Motoneurons of the Rat

1997 ◽  
Vol 78 (5) ◽  
pp. 2246-2253 ◽  
Author(s):  
Andrea Sawczuk ◽  
Randall K. Powers ◽  
Marc D. Binder
Keyword(s):  
Outward Current ◽  
Spike Frequency ◽  
Bathing Solution ◽  
Spike Frequency Adaptation ◽  
Cellular Mechanisms ◽  
Hypoglossal Motoneurons ◽  
Frequency Adaptation ◽  
Outward Currents ◽  
Bath Application ◽  
Sustained Discharge

Sawczuk, Andrea, Randall K. Powers, and Marc D. Binder. Contribution of outward currents to spike-frequency adaptation in hypoglossal motoneurons of the rat. J. Neurophysiol. 78: 2246–2253, 1997. Spike-frequency adaptation has been attributed to the actions of several different membrane currents. In this study, we assess the contributions of two of these currents: the net outward current generated by the electrogenic Na+-K+ pump and the outward current that flows through Ca2+-activated K+ channels. In recordings made from hypoglossal motoneurons in slices of rat brain stem, we found that bath application of a 4–20 μM ouabain solution produced a partial block of Na+-K+ pump activity as evidenced by a marked reduction in the postdischarge hyperpolarization that follows a period of sustained discharge. However, we observed no significant change in either the initial, early, or late phases of spike-frequency adaptation in the presence of ouabain. Adaptation also has been related to increases in the duration and magnitude of the medium-duration afterhyperpolarization (mAHP) mediated by Ca2+-activated K+ channels. When we replaced the 2 mM Ca2+ in the bathing solution with Mn2+, there was a significant decrease in the amplitude of the mAHP after a spike. The decrease in mAHP amplitude resulted in a decrease in the magnitude of the initial phase of spike-frequency adaptation as has been reported previously by others. However, quite unexpectedly we also found that reducing the mAHP resulted in a dramatic increase in the magnitude of both the early and late phases of adaptation. These changes could be reversed by restoring the normal Ca2+ concentration in the bath. Our results with ouabain indicate that the Na+-K+ pump plays little, if any, role in the three phases of adaptation in rat hypoglossal motoneurons. Our results with Ca2+ channel blockade support the hypothesis that initial adaptation is, in part, controlled by conductances underlying the mAHP. However, our failure to eliminate initial adaptation completely by blocking Ca2+ channels suggests that other membrane mechanisms also contribute. Finally, the increase in both the early and late phases of adaptation in the presence of Mn2+ block of Ca2+ channels lends further support to the hypothesis that the initial and later (i.e., early and late) phases of spike-frequency adaptation are mediated by different cellular mechanisms.

Electrophysiology of mammalian tectal neurons in vitro. II. Long-term adaptation

1988 ◽  
Vol 60 (3) ◽  
pp. 869-878 ◽  
Author(s):  
R. Llinás ◽  
J. Lopez-Barneo
Keyword(s):  
Time Constant ◽  
Action Potentials ◽  
Time Course ◽  
Stimulus Frequency ◽  
Spike Frequency ◽  
Repetitive Firing ◽  
Spike Frequency Adaptation ◽  
Frequency Adaptation ◽  
Slow Kinetics

1. The long-term adaptation of repetitive firing in guinea pig superior colliculus neurons was studied in a mesencephalic slice preparation using intracellular recording techniques. 2. This long-term adaptation was characterized by a decrease in the number of action potentials generated by a depolarizing pulse of constant amplitude applied at frequencies of 0.5-2 Hz. Long-term adaptation appeared in all cells tested regardless of whether they showed short-term spike frequency adaptation during each pulse. 3. Long-term adaptation had a close-to-exponential time course with a time constant of 4.085 +/- 0.675 s (mean +/- SD, n = 8). This phenomenon developed more rapidly as the stimulus frequency increased and was paralleled by a progressive hyperpolarization of the membrane potential which, at the termination of the train of stimuli, remained 6-10 mV more negative than the resting value. 4. The hyperpolarization and the spike frequency adaptation recovered spontaneously in approximately 60 s. The time constant of recovery was 14.66 +/- 1.189 s (n = 4). 5. The afterhyperpolarization (AHP) was also paralleled by a decrease in the input resistance of the cells. This response and the adaptation disappeared after removal of Ca2+ or after addition of Cd2+ to the external solution. This suggests that Ca2+ entry during trains of action potentials activates a Ca2+-dependent K+ conductance with an unusually slow kinetics. 6. This conductance appears to differ from other Ca2+-dependent K+ conductances in that it was blocked by 4-aminopyridine. 7. The properties of this long-term adaptation are remarkably similar to those reported for visual habituation; thus this newly described K+ conductance may be pertinent to the understanding of this behavioral phenomenon.

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.

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)

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.

A Model of Reverse Spike Frequency Adaptation and Repetitive Firing of Subthalamic Nucleus Neurons

2004 ◽  
Vol 91 (5) ◽  
pp. 1963-1980 ◽  
Author(s):  
Charles J. Wilson ◽  
Angela Weyrick ◽  
David Terman ◽  
Nicholas E. Hallworth ◽  
Mark D. Bevan
Keyword(s):  
Steady State ◽  
Subthalamic Nucleus ◽  
Spike Frequency ◽  
Calcium Currents ◽  
Repetitive Firing ◽  
Spike Frequency Adaptation ◽  
Firing Rates ◽  
Spike Threshold ◽  
Secondary Range ◽  
Frequency Adaptation

Subthalamic nucleus neurons exhibit reverse spike-frequency adaptation. This occurs only at firing rates of 20–50 spikes/s and higher. Over this same frequency range, there is an increase in the steady-state frequency–intensity ( F– I) curve's slope (the secondary range). Specific blockade of high-voltage activated calcium currents reduced the F– I curve slope and reverse adaptation. Blockade of calcium-dependent potassium current enhanced secondary range firing. A simple model that exhibited these properties used spike-triggered conductances similar to those in subthalamic neurons. It showed: 1) Nonaccumulating spike afterhyperpolarizations produce positively accelerating F– I curves and spike-frequency adaptation that is complete after the second spike. 2) Combinations of accumulating aftercurrents result in a linear F– I curve, whose slope depends on the relative contributions of inward and outward currents. Spike-frequency adaptation can be gradual. 3) With both accumulating and nonaccumulating aftercurrents, primary and secondary ranges will be present in the F– I curve. The slope of the primary range is determined by the nonaccumulating conductance; the accumulating conductances govern the secondary range. The transition is determined by the relative strengths of accumulating and nonaccumulating currents. 4) Spike-threshold accommodation contributes to the secondary range, reducing its slope at high firing rates. Threshold accommodation can stabilize firing when inward aftercurrents exceed outward ones. 5) Steady-state reverse adaptation results when accumulated inward aftercurrents exceed outward ones. This requires spike-threshold accommodation. Transient speedup arises when inward currents are smaller than outward ones at steady state, but accumulate more rapidly. 6) The same mechanisms alter firing in response to irregular patterns of synaptic conductances, as cell excitability fluctuates with changes in firing rate.

Encoder Adaptation Modulates the Visual Responses of Crayfish Interneurons

2004 ◽  
Vol 92 (1) ◽  
pp. 327-340 ◽  
Author(s):  
Raymon M. Glantz ◽  
John P. Schroeter
Keyword(s):  
Firing Rate ◽  
Time Course ◽  
Light Flash ◽  
Time Derivative ◽  
Input Resistance ◽  
Spike Frequency ◽  
Visual Response ◽  
Spike Frequency Adaptation ◽  
Visual Responses ◽  
Frequency Adaptation

The responses of sustaining and dimming fibers were characterized by the time varying firing rates elicited by extrinsic current and flashes of light. These data were simulated by an adaptive integrate-and-fire model. A postimpulse shunt conductance simulated spike-frequency adaptation. The correlation between observed and model current-elicited impulse rates was 0.94–0.98. However, except for a difference in input resistance (both measured and simulated), the voltage to impulse encoders of the two cell groups was similar and exhibited comparable degrees of spike-frequency adaptation (40 to 45%). The encoder model derived from current-elicited responses (with fixed parameters) was used to simulate visual responses elicited by light flashes. These simulations included a synaptic current derived from the time course of the postsynaptic potential (PSP). The sustaining fiber visual response consisted of a large excitatory PSP and high-frequency transient burst that adapted (by ∼80%) to a low-frequency plateau discharge. The simulations indicated that spike-frequency adaptation had no effect on the transient discharge but reduced the plateau firing rate by ∼60%. Encoder adaptation enhances the sustaining fiber response to the time derivative of the stimulus. In dimming fibers, the light flash elicits an inhibitory PSP that interrupts the “dark discharge” and an off response following the end of the flash. The simulations indicated that spike-frequency adaptation reduces the firing rate of both the dark discharge and the off response. Thus the model suggests that different effects of encoder adaptation on the two cell types arise from the same encoder mechanisms, but different actions are determined by differences in impulse rate and the time course of the discharge.

Current and Voltage Clamp Studies of the Spike Medium Afterhyperpolarization of Hypoglossal Motoneurons in a Rat Brain Stem Slice Preparation

2000 ◽  
Vol 83 (5) ◽  
pp. 2987-2995 ◽  
Author(s):  
Remigijus Lape ◽  
Andrea Nistri
Keyword(s):  
Membrane Potential ◽  
Brain Stem ◽  
Voltage Clamp ◽  
Current Pulse ◽  
Spike Frequency ◽  
Spike Frequency Adaptation ◽  
Slice Preparation ◽  
Firing Behavior ◽  
Hypoglossal Motoneurons ◽  
Frequency Adaptation

Whole-cell patch clamp recordings were performed on hypoglossal motoneurons (HMs) in a brain stem slice preparation from the neonatal rat. The medium afterhyperpolarization (mAHP) was the only afterpotential always present after single or multiple spikes, making it suitable for studying its role in firing behavior. At resting membrane potential (−68.8 ± 0.7 mV), mAHP (23 ± 2 ms rise-time and 150 ± 10 ms decay) had 9.5 ± 0.7 mV amplitude, was suppressed in Ca2+-free medium or by 100 nM apamin, and reversed at −94 mV membrane potential. These observations suggest that mAHP was due to activation of Ca2+-dependent, SK-type K+ channels. Carbachol (10–100 μM) reversibly and dose dependently blocked the mAHP and depolarized HMs (both effects prevented by 10 μM atropine). Similar mAHP block was produced by muscarine (50 μM). In control solution a constant current pulse (1 s) induced HM repetitive firing with small spike frequency adaptation. When the mAHP was blocked by apamin, the same current pulse evoked much higher frequency firing with strong spike frequency adaptation. Carbachol also elicited faster firing and adapting behavior. Voltage clamp experiments demonstrated a slowly deactivating, apamin-sensitive K+ current ( I AHP) which could account for the mAHP. I AHP reversed at −94 mV membrane potential, was activated by depolarization as short as 1 ms, decayed with a time constant of 154 ± 9 ms at −50 mV, and was also blocked by 50 μM carbachol. These data suggest that mAHP had an important role in controlling firing behavior as clearly demonstrated after its pharmacological block and was potently modulated by muscarinic receptor activity.

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