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Energy substrates that fuel fast neuronal network oscillations.

Galow LV, Schneider J, Lewen A, Ta TT, Papageorgiou IE, Kann O - Front Neurosci (2014)

Bottom Line: This preparation permits superior oxygen supply as well as fast application of glucose, glycolytic metabolites or drugs such as glycogen phosphorylase inhibitor during extracellular recordings of the local field potential.However, when glucose is present, the turnover of glycogen is not essential to sustain gamma oscillations.Our study shows that fast neuronal network oscillations can be fueled by different energy-rich substrates, with glucose being most effective.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology and Pathophysiology and Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg Heidelberg, Germany.

ABSTRACT
Fast neuronal network oscillations in the gamma-frequency band (30--100 Hz) provide a fundamental mechanism of complex neuronal information processing in the hippocampus and neocortex of mammals. Gamma oscillations have been implicated in higher brain functions such as sensory perception, motor activity, and memory formation. The oscillations emerge from precise synapse interactions between excitatory principal neurons such as pyramidal cells and inhibitory GABAergic interneurons, and they are associated with high energy expenditure. However, both energy substrates and metabolic pathways that are capable to power cortical gamma oscillations have been less defined. Here, we investigated the energy sources fueling persistent gamma oscillations in the CA3 subfield of organotypic hippocampal slice cultures of the rat. This preparation permits superior oxygen supply as well as fast application of glucose, glycolytic metabolites or drugs such as glycogen phosphorylase inhibitor during extracellular recordings of the local field potential. Our findings are: (i) gamma oscillations persist in the presence of glucose (10 mmol/L) for greater than 60 min in slice cultures while (ii) lowering glucose levels (2.5 mmol/L) significantly reduces the amplitude of the oscillation. (iii) Gamma oscillations are absent at low concentration of lactate (2 mmol/L). (iv) Gamma oscillations persist at high concentration (20 mmol/L) of either lactate or pyruvate, albeit showing significant reductions in the amplitude. (v) The breakdown of glycogen significantly delays the decay of gamma oscillations during glucose deprivation. However, when glucose is present, the turnover of glycogen is not essential to sustain gamma oscillations. Our study shows that fast neuronal network oscillations can be fueled by different energy-rich substrates, with glucose being most effective.

No MeSH data available.


Related in: MedlinePlus

Gamma oscillations and glycogen stores during glucose deprivation. (A) Gamma oscillations were induced by bath application of acetylcholine (2 μmol/L) and physostigmine (400 nmol/L) in the presence of 10 mmol/L glucose (white bar). Subsequently, inhibitors of glycogen phosphorylase, DAB (50 μmol/l or 100 μmol/L) or CP-316819 (10 μmol/L or 20 μmol/L) were applied, in the presence (black bar) or absence (light blue bar) of glucose. Note that the standard gas mixture (95% O2 and 5% CO2) was continuously present. Local field potentials (LFP) were recorded in stratum pyramidale of the CA3 subfield subfield (sample trace). (B) The peak power spectral density (μV2/Hz) for each recording trace is shown in black (scaling on left y-axis), the average of all recordings is shown in blue (scaling on right y-axis). Power spectra were calculated every 10 s and plotted over time. (C) The points in time are given for complete suppression of gamma oscillations, i.e., power reaching a threshold defined as the mean of the last 100 s plus 1 standard deviation, according to the protocol given in (A) (control, n = 10, N = 3; DAB, n = 6, N = 3, and n = 5, N = 3; CP-316819, n = 6, N = 3, and n = 5, N = 2). Note that inhibition of glycogen phosphorylase accelerates the decay of gamma oscillations during glucose deprivation. Kruskal Wallis ANOVA on ranks. Statistical significance vs. control is marked by asterisks (P < 0.05).
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Figure 6: Gamma oscillations and glycogen stores during glucose deprivation. (A) Gamma oscillations were induced by bath application of acetylcholine (2 μmol/L) and physostigmine (400 nmol/L) in the presence of 10 mmol/L glucose (white bar). Subsequently, inhibitors of glycogen phosphorylase, DAB (50 μmol/l or 100 μmol/L) or CP-316819 (10 μmol/L or 20 μmol/L) were applied, in the presence (black bar) or absence (light blue bar) of glucose. Note that the standard gas mixture (95% O2 and 5% CO2) was continuously present. Local field potentials (LFP) were recorded in stratum pyramidale of the CA3 subfield subfield (sample trace). (B) The peak power spectral density (μV2/Hz) for each recording trace is shown in black (scaling on left y-axis), the average of all recordings is shown in blue (scaling on right y-axis). Power spectra were calculated every 10 s and plotted over time. (C) The points in time are given for complete suppression of gamma oscillations, i.e., power reaching a threshold defined as the mean of the last 100 s plus 1 standard deviation, according to the protocol given in (A) (control, n = 10, N = 3; DAB, n = 6, N = 3, and n = 5, N = 3; CP-316819, n = 6, N = 3, and n = 5, N = 2). Note that inhibition of glycogen phosphorylase accelerates the decay of gamma oscillations during glucose deprivation. Kruskal Wallis ANOVA on ranks. Statistical significance vs. control is marked by asterisks (P < 0.05).

Mentions: We further explored whether glycogen breakdown is capable to fuel gamma oscillations. Glycogen stores have been described in astrocytes and, more recently, also in neurons (Choi et al., 2012; Dienel and Cruz, 2014; Saez et al., 2014). At first, we determined the time course of suppression of gamma oscillations during glucose deprivation in the presence of 95% oxygen fraction (Figures 6A–C). Activity was completely suppressed after 29 ± 1 min (n = 10) in recording solution with 0 mmol/L glucose (data not shown). This time course reflects utilization of various energy reserves such as glycogen for ATP generation in different pathways (Roberts, 2007; Dienel and Cruz, 2014) and, presumably, a considerable glycogen reserve in slice cultures (Cater et al., 2001).


Energy substrates that fuel fast neuronal network oscillations.

Galow LV, Schneider J, Lewen A, Ta TT, Papageorgiou IE, Kann O - Front Neurosci (2014)

Gamma oscillations and glycogen stores during glucose deprivation. (A) Gamma oscillations were induced by bath application of acetylcholine (2 μmol/L) and physostigmine (400 nmol/L) in the presence of 10 mmol/L glucose (white bar). Subsequently, inhibitors of glycogen phosphorylase, DAB (50 μmol/l or 100 μmol/L) or CP-316819 (10 μmol/L or 20 μmol/L) were applied, in the presence (black bar) or absence (light blue bar) of glucose. Note that the standard gas mixture (95% O2 and 5% CO2) was continuously present. Local field potentials (LFP) were recorded in stratum pyramidale of the CA3 subfield subfield (sample trace). (B) The peak power spectral density (μV2/Hz) for each recording trace is shown in black (scaling on left y-axis), the average of all recordings is shown in blue (scaling on right y-axis). Power spectra were calculated every 10 s and plotted over time. (C) The points in time are given for complete suppression of gamma oscillations, i.e., power reaching a threshold defined as the mean of the last 100 s plus 1 standard deviation, according to the protocol given in (A) (control, n = 10, N = 3; DAB, n = 6, N = 3, and n = 5, N = 3; CP-316819, n = 6, N = 3, and n = 5, N = 2). Note that inhibition of glycogen phosphorylase accelerates the decay of gamma oscillations during glucose deprivation. Kruskal Wallis ANOVA on ranks. Statistical significance vs. control is marked by asterisks (P < 0.05).
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Figure 6: Gamma oscillations and glycogen stores during glucose deprivation. (A) Gamma oscillations were induced by bath application of acetylcholine (2 μmol/L) and physostigmine (400 nmol/L) in the presence of 10 mmol/L glucose (white bar). Subsequently, inhibitors of glycogen phosphorylase, DAB (50 μmol/l or 100 μmol/L) or CP-316819 (10 μmol/L or 20 μmol/L) were applied, in the presence (black bar) or absence (light blue bar) of glucose. Note that the standard gas mixture (95% O2 and 5% CO2) was continuously present. Local field potentials (LFP) were recorded in stratum pyramidale of the CA3 subfield subfield (sample trace). (B) The peak power spectral density (μV2/Hz) for each recording trace is shown in black (scaling on left y-axis), the average of all recordings is shown in blue (scaling on right y-axis). Power spectra were calculated every 10 s and plotted over time. (C) The points in time are given for complete suppression of gamma oscillations, i.e., power reaching a threshold defined as the mean of the last 100 s plus 1 standard deviation, according to the protocol given in (A) (control, n = 10, N = 3; DAB, n = 6, N = 3, and n = 5, N = 3; CP-316819, n = 6, N = 3, and n = 5, N = 2). Note that inhibition of glycogen phosphorylase accelerates the decay of gamma oscillations during glucose deprivation. Kruskal Wallis ANOVA on ranks. Statistical significance vs. control is marked by asterisks (P < 0.05).
Mentions: We further explored whether glycogen breakdown is capable to fuel gamma oscillations. Glycogen stores have been described in astrocytes and, more recently, also in neurons (Choi et al., 2012; Dienel and Cruz, 2014; Saez et al., 2014). At first, we determined the time course of suppression of gamma oscillations during glucose deprivation in the presence of 95% oxygen fraction (Figures 6A–C). Activity was completely suppressed after 29 ± 1 min (n = 10) in recording solution with 0 mmol/L glucose (data not shown). This time course reflects utilization of various energy reserves such as glycogen for ATP generation in different pathways (Roberts, 2007; Dienel and Cruz, 2014) and, presumably, a considerable glycogen reserve in slice cultures (Cater et al., 2001).

Bottom Line: This preparation permits superior oxygen supply as well as fast application of glucose, glycolytic metabolites or drugs such as glycogen phosphorylase inhibitor during extracellular recordings of the local field potential.However, when glucose is present, the turnover of glycogen is not essential to sustain gamma oscillations.Our study shows that fast neuronal network oscillations can be fueled by different energy-rich substrates, with glucose being most effective.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology and Pathophysiology and Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg Heidelberg, Germany.

ABSTRACT
Fast neuronal network oscillations in the gamma-frequency band (30--100 Hz) provide a fundamental mechanism of complex neuronal information processing in the hippocampus and neocortex of mammals. Gamma oscillations have been implicated in higher brain functions such as sensory perception, motor activity, and memory formation. The oscillations emerge from precise synapse interactions between excitatory principal neurons such as pyramidal cells and inhibitory GABAergic interneurons, and they are associated with high energy expenditure. However, both energy substrates and metabolic pathways that are capable to power cortical gamma oscillations have been less defined. Here, we investigated the energy sources fueling persistent gamma oscillations in the CA3 subfield of organotypic hippocampal slice cultures of the rat. This preparation permits superior oxygen supply as well as fast application of glucose, glycolytic metabolites or drugs such as glycogen phosphorylase inhibitor during extracellular recordings of the local field potential. Our findings are: (i) gamma oscillations persist in the presence of glucose (10 mmol/L) for greater than 60 min in slice cultures while (ii) lowering glucose levels (2.5 mmol/L) significantly reduces the amplitude of the oscillation. (iii) Gamma oscillations are absent at low concentration of lactate (2 mmol/L). (iv) Gamma oscillations persist at high concentration (20 mmol/L) of either lactate or pyruvate, albeit showing significant reductions in the amplitude. (v) The breakdown of glycogen significantly delays the decay of gamma oscillations during glucose deprivation. However, when glucose is present, the turnover of glycogen is not essential to sustain gamma oscillations. Our study shows that fast neuronal network oscillations can be fueled by different energy-rich substrates, with glucose being most effective.

No MeSH data available.


Related in: MedlinePlus