Pka mediates the effects of monoamine transmitters on the K+ current underlying the slow spike frequency adaptation in hippocampal neurons

Neuron ◽  
1993 ◽  
Vol 11 (6) ◽  
pp. 1023-1035 ◽  
Author(s):  
Paola Pedarzani ◽  
Johan F. Storm
Keyword(s):  
Hippocampal Neurons ◽  
Spike Frequency ◽  
Spike Frequency Adaptation ◽  
Frequency Adaptation ◽  
K Current ◽  
Monoamine Transmitters

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.

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.

Morphological and Electrophysiological Properties of Principal Neurons in the Rat Lateral Amygdala In Vitro

2001 ◽  
Vol 85 (2) ◽  
pp. 714-723 ◽  
Author(s):  
E.S.L. Faber ◽  
R. J. Callister ◽  
P. Sah
Keyword(s):  
Cell Morphology ◽  
Brain Slices ◽  
Spike Trains ◽  
Spike Frequency ◽  
Morphological Properties ◽  
Spike Frequency Adaptation ◽  
Differential Distribution ◽  
Lateral Amygdala ◽  
Frequency Adaptation ◽  
Firing Properties

In this study, we characterize the electrophysiological and morphological properties of spiny principal neurons in the rat lateral amygdala using whole cell recordings in acute brain slices. These neurons exhibited a range of firing properties in response to prolonged current injection. Responses varied from cells that showed full spike frequency adaptation, spiking three to five times, to those that showed no adaptation. The differences in firing patterns were largely explained by the amplitude of the afterhyperpolarization (AHP) that followed spike trains. Cells that showed full spike frequency adaptation had large amplitude slow AHPs, whereas cells that discharged tonically had slow AHPs of much smaller amplitude. During spike trains, all cells showed a similar broadening of their action potentials. Biocytin-filled neurons showed a range of pyramidal-like morphologies, differed in dendritic complexity, had spiny dendrites, and differed in the degree to which they clearly exhibited apical versus basal dendrites. Quantitative analysis revealed no association between cell morphology and firing properties. We conclude that the discharge properties of neurons in the lateral nucleus, in response to somatic current injections, are determined by the differential distribution of ionic conductances rather than through mechanisms that rely on cell morphology.

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)

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