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Cited by 98Mitochondrial Function and PathologyNeuroscience and Neuropharmacology ResearchNeural dynamics and brain function

Coupling of neuronal activity and mitochondrial metabolism as revealed by NAD(P)H fluorescence signals in organotypic hippocampal slice cultures of the rat

Kann, O, Schuchmann, S, Buchheim, K, Heinemann, U·2003·Neuroscience
DOI 10.1016/s0306-4522(03)00026-5
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Abstract

During physiological activity neurons may experience localised energy demands which require intracellular signals for stimulation of mitochondrial NADH generation and subsequent delivery of ATP. To elucidate these mechanisms, we applied microfluorimetric monitoring of cytoplasmic (Fluo-3) and mitochondrial (Rhod-2) calcium concentration ([Ca(2+)](c), [Ca(2+)](m)), as well as of mitochondrial oxidative metabolism (NAD(P)H), whilst simultaneously measuring changes in extracellular potassium concentration ([K(+)](o)), as an indicator of neuronal activity in hippocampal slice cultures. Changes in neuronal activity were induced by repetitive stimulation at different frequencies (5, 20, 100 Hz) and intensities. Stimulation parameters were chosen to elicit rises in [K(+)](o) of less than 3 mM which is comparable to physiologically occurring rises in [K(+)](o). The mitochondrial uncoupler carbonyl cyanide m-chlorophenyl hydrazone (CCCP) reduced stimulus-induced changes in Rhod-2 fluorescence by 79%, indicating that Rhod-2 signals were primarily of mitochondrial origin. Repetitive stimulation at 20 Hz applied to areas CA1 or CA3 resulted in moderate rises in [K(+)](o) which were associated with stimulus-dependent elevations in [Ca(2+)](c) and [Ca(2+)](m) of up to 15%. The same stimuli also elicited biphasic changes in NAD(P)H fluorescence characterised by an initial decline and a subsequent prolonged elevation of up to 10%. Variation of stimulus parameters revealed close correlations between rises in [K(+)](o), in [Ca(2+)](m) and changes in NAD(P)H fluorescence. To elucidate the role of intracellular Ca(2+) accumulation in induction of NAD(P)H fluorescence signals, the effect of application of Ca(2+)-free solution on these signals evoked by repetitive antidromic stimulation of the alveus during recordings in area CA1 was studied. Lowering extracellular Ca(2+) led to complete blockade of postsynaptic field potential components as well as of rises in [Ca(2+)](c) and [Ca(2+)](m). Amplitudes of NAD(P)H signals were reduced by 59%, though rises in [K(+)](o) were comparable in presence and absence of extracellular Ca(2+). The results suggest i) that mitochondrial oxidative metabolism is fine-tuned to graded physiological activity in neurons and ii) that rapid mitochondrial Ca(2+) signalling represents one of the main determinants for stimulation of oxidative metabolism under physiological conditions.

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  • Upon stimulation of neurons in a brain slice or individual dissociated neurons, the NAD(P)H signal has a stereotyped response: a rapid dip in fluorescence within the first few seconds that yields in ∼10 s to a prolonged increase above baseline (overshoot) lasting for 2-3 min.

    “Upon stimulation of neurons in a brain slice (Kann et al., 2003; Shuttleworth et al., 2003; Kasischke et al., 2004) or individual dissociated neurons (Duchen, 1992), the NAD(P)H signal has a stereotyped response: a rapid dip in fluorescence occurring within the first few seconds that yields in ∼10 s to a prolonged increase above baseline (overshoot) lasting for 2–3 min (Fig. 2 B).”

    From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Kann et al., 2003

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Authors
Kann, O., Schuchmann, S., Buchheim, K., & Heinemann, U.
Affiliations
Humboldt-Universität zu Berlin (DE)
Corresponding author
Kann, O
ORCID
Kann, O
Venue
Neuroscience
Publisher
Elsevier BV
Published
2003-06
Volume
119
Issue
1
Pages
87-100
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/s0306-4522(03)00026-5
OpenAlex
W2030286287
Cited by
98
References
65
Citations by year
2026: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 4 · 2016: 5 · 2015: 7 · 2014: 3 · 2013: 2 · 2012: 5
FWCI
3.12
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
neuronal activity, mitochondrial metabolism, NAD(P)H fluorescence, hippocampal slice cultures, extracellular potassium, mitochondrial calcium, intracellular calcium, repetitive stimulation, CCCP, CA1, CA3, energy metabolism
MeSH terms
Aniline Compounds, Animals, Animals, Newborn, Calcium, Carbonyl Cyanide m-Chlorophenyl Hydrazone, Cells, Cultured, Dose-Response Relationship, Drug, Electric Stimulation, Fluorescent Dyes, Heterocyclic Compounds, 3-Ring, Hippocampus, Ionophores, Membrane Potentials, Mitochondria, NADP, Neurons, Potassium, Xanthenes, Rats, Wistar, Ion-Selective Electrodes, Rats, In Vitro Techniques

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