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Relationship between repetitive firing and afterhyperpolarizations in human neocortical neurons
Abstract
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.
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“increases excitability via Ca2+-dependent potassium channels177–179”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [177]
In the citing paper
“AHP currents are mainly mediated by calcium-dependent potassium channels [77, 78], but also partly by calcium-independent potassium channels [79].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [79]
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“…the conductances underlying the slow component of the AHP in cortical neurons, such as the Ca-dependent K+ current (IAHP), the voltage-gated K+ current (IM), and slow Ca-dependent and Na-dependent K+ currents hav been implicated in altering spike frequency adaptation (Lorenzon & Foehring, 1992).”
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Deisz, R. A., & Luhmann, H. J. (1995) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195083309.003.0016 · Cited by 8
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“Well-known examples include the afterhyperpolarizing (AHP) potassium ion currents found in mammalian neocortical neurons (Lorenzon and Foehring 1992; Sanchez-Vives et al. 2000b).”
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“1 C ; Foehring et al., 1991; Lorenzon and Foehring, 1992; Varga et al., 2015; Eyal et al., 2018).”
InfluentialSpike-frequency adaptation as a mechanism for dynamic coding in V1
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Expósito, S., Alberquilla, S., & Martín, E. D. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.24.576973 · Cited by 3
“Three AHP components are widely described in rodent and humans 2,5–8 .”
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Characterizing the diversity of L2/3 human neocortical neurons in epilepsyPreprint
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“Three AHP components have been widely described in both rodents and humans (Lorenzon and Foehring, 1992; Schwindt et al., 1988; Storm, 1987, 1989, 1990).”
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“…(SK) and the large-conductance (BK) channels can contribute to overall network excitability via their roles in generating action potential afterhyperpolarizations (AHPs) (Avoli and Olivier, 1989; Faber and Sah, 2002; Higgs and Spain, 2009; Lorenzon and Foehring, 1992; Zang et al., 2018).”
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Meng, J. H., Kang, Y., Lai, A., Feyerabend, M., Inoue, W., Martínez-Trujillo, J., Rudy, B., & Wang, X. (2026) · iScience · doi:10.1016/j.isci.2026.117712 · Cited by 2
Metadata
- Authors
- Lorenzon, N. M., & Foehring, R. C.
- Affiliations
- Department of Anatomy and Neurobiology, University of Tennessee,Memphis 38103-4901.
- ORCID
- Foehring, R. C.
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 1992-02-01
- Volume
- 67
- Issue
- 2
- Pages
- 350-363
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W2399267155
- Cited by
- 145
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 4
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29ns027180-05)
- National Institute of Neurological Disorders and Stroke (R29 NS-27180)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- afterhyperpolarization, repetitive firing, spike frequency adaptation, calcium-activated potassium current, tetraethylammonium, apamin, muscarinic receptors, norepinephrine, serotonin, habituation, in vitro slice preparation, intracellular recording
- MeSH terms
- Action Potentials, Apamin, Cerebral Cortex, Cobalt, Electrophysiology, Epilepsy, Humans, Ion Channels, Membrane Potentials, Microelectrodes, Neural Conduction, Neurons, Serotonin, Tetraethylammonium Compounds, 4-Aminopyridine, In Vitro Techniques
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