Highly energized inhibitory interneurons are a central element for information processing in cortical networks.
Open accessAbstract
Gamma oscillations (~30 to 100 Hz) provide a fundamental mechanism of information processing during sensory perception, motor behavior, and memory formation by coordination of neuronal activity in networks of the hippocampus and neocortex. We review the cellular mechanisms of gamma oscillations about the underlying neuroenergetics, i.e., high oxygen consumption rate and exquisite sensitivity to metabolic stress during hypoxia or poisoning of mitochondrial oxidative phosphorylation. Gamma oscillations emerge from the precise synaptic interactions of excitatory pyramidal cells and inhibitory GABAergic interneurons. In particular, specialized interneurons such as parvalbumin-positive basket cells generate action potentials at high frequency (‘fast-spiking’) and synchronize the activity of numerous pyramidal cells by rhythmic inhibition (‘clockwork’). As prerequisites, fast-spiking interneurons have unique electrophysiological properties and particularly high energy utilization, which is reflected in the ultrastructure by enrichment with mitochondria and cytochrome c oxidase, most likely needed for extensive membrane ion transport and γ-aminobutyric acid metabolism. This supports the hypothesis that highly energized fast-spiking interneurons are a central element for cortical information processing and may be critical for cognitive decline when energy supply becomes limited (‘interneuron energy hypothesis’). As a clinical perspective, we discuss the functional consequences of metabolic and oxidative stress in fast-spiking interneurons in aging, ischemia, Alzheimer's disease, and schizophrenia.
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PV cells are particularly susceptible to oxidative stress given their fast cellular metabolism and increased mitochondrial function.
“PV cells are particularly susceptible to oxidative stress given their fast cellular metabolism and increased mitochondrial function (Hasenstaub et al., 2010; Kann et al., 2014; Inan et al., 2016).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Kann et al., 2014
The energy demands of PV-INs make them highly susceptible to loss of mitochondrial membrane potential and to metabolic and oxidative stress that accompanies disease states.
“The energy requirements of PV-INs make them highly susceptible to the loss of mitochondrial membrane potential (a component of, and a proxy for, a decrease in mitochondrial function), and to metabolic and oxidative stress that accompanies disease states [81,91].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [81]
A substantial amount of cytochrome c and cytochrome c oxidase supports the high bioenergetic needs of PV-INs, but cytochrome c is also central to apoptosis induction.
“A substantial quantity of cytochrome c and cytochrome c oxidase supports the high bioenergetic needs of PV-INs [81,85], but comes at a price as cytochrome c is also central to the induction of apoptosis [86].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [81]
PV-INs have extraordinary energy requirements to support high metabolic activity and to protect against significant glutamatergic stress.
“PV-INs have extraordinary energy requirements to support a high metabolic activity and to protect against significant glutamatergic stress [16,80,81].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [81]
The large amounts of ATP needed to sustain gamma oscillations are supplied by a high density of mitochondria.
“The large amounts of ATP needed to sustain gamma oscillations are supplied by a high density of mitochondria [81][82][83].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [81]
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- Authors
- Kann, O., Papageorgiou, I. E., & Draguhn, A.
- Affiliations
- Heidelberg University (DE)
- Corresponding author
- Kann, Oliver
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2014-06-04
- Volume
- 34
- Issue
- 8
- Pages
- 1270-1282
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC4126088
- OpenAlex
- W2091536100
- Cited by
- 295
- References
- 191
- Citations by year
- 2026: 29 · 2025: 38 · 2024: 31 · 2023: 27 · 2022: 23 · 2021: 23 · 2020: 26 · 2019: 24 · 2018: 21 · 2017: 13 · 2016: 18 · 2015: 18 · 2014: 3
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- gamma oscillations, fast-spiking interneurons, cortical processing, neuroenergetics, mitochondrial oxidative phosphorylation, hypoxia, metabolic stress, GABAergic inhibition, pyramidal neurons, cytochrome c oxidase, mitochondrial ultrastructure, aging, ischemia, Alzheimer's disease, schizophrenia
- MeSH terms
- Animals, Energy Metabolism, Hippocampus, Humans, Interneurons, Nerve Net, Neural Inhibition, Oxygen, Oxidative Stress, Neocortex, Inhibitory Postsynaptic Potentials
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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