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The modulation of nicotinic acetylcholine receptors on the neuronal network oscillations in rat hippocampal CA3 area.

Wang Y, Wang Z, Wang J, Wang Y, Henderson Z, Wang X, Zhang X, Song J, Lu C - Sci Rep (2015)

Bottom Line: Nicotine enhanced γ oscillation at concentrations of 0.1-10 μM, but reduced it at a higher concentration of 100 μM.However, these nAChR antagonists failed to block the suppressing role of nicotine on γ.Furthermore, we found that the NMDA receptor antagonist D-AP5 completely blocked the effect of nicotine.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory for the Brain Research of Henan Province, Xinxiang Medical University, Henan Province, Henan PR. China.

ABSTRACT
γ oscillations are associated with higher brain functions such as memory, perception and consciousness. Disruption of γ oscillations occur in various neuro-psychological disorders such as schizophrenia. Nicotinic acetylcholine receptors (nAChR) are highly expressed in the hippocampus, however, little is known about the role on hippocampal persistent γ oscillation. This study examined the effects of nicotine and selective nAChR agonists and antagonists on kainate-induced persistent γ oscillation in rat hippocampal slices. Nicotine enhanced γ oscillation at concentrations of 0.1-10 μM, but reduced it at a higher concentration of 100 μM. The enhancement on γ oscillation can be best mimicked by co-application of α4β2- and α7-nAChR agonist and reduced by a combination of nAChR antagonists, DhβE and MLA. However, these nAChR antagonists failed to block the suppressing role of nicotine on γ. Furthermore, we found that the NMDA receptor antagonist D-AP5 completely blocked the effect of nicotine. These results demonstrate that nicotine modulates γ oscillations via α7 and α4β2 nAChR as well as NMDA activation, suggesting that nAChR activation may have a therapeutic role for the clinical disorder such as schizophrenia, which is known to have impaired γ oscillation and hypo-NMDA receptor function.

No MeSH data available.


Related in: MedlinePlus

The effects of nicotine on γ oscillations.(A1–C1) KA-induced γ oscillation. (A1): Representative traces of extracellular recordings in hippocampal CA3 before and after KA application; The 1-second waveforms were taken from the steady states before and after application of KA. (B1): The power spectra of the field potentials before and after application of KA; (C1): The time course shows the changes of γ power before and after application of KA. (A2–A5) Representative extracellular recordings of field potentials before and after application of nicotine at 0.25 μM (A2), 1 μM (A3), 10 μM (A4) and 100 μM (A5). (B2–B5) Power spectra of field potentials before and after application of nicotine at 0.25 μM (B2), 1 μM (B3), 10 μM (B4) and 100 μM (B5); (C2–C5) The time courses showing the changes of γ power before and after application of nicotine at 0.25 μM (C2); 1 μM (C3), 10 μM (C4) and 100 μM (C5). (D): Bar graph summarizes the percent changes in γ power before and after application of various concentrations of nicotine. Gray bar: Normalized γ power in control (100%, KA alone). Black bars: The percent changes in γ powers after application of various concentrations of nicotine. *p < 0.05, **p < 0.01, ***p < 0.001, compared with control, one way RM ANOVA, n = 9, 13, 10, 10 for 0.25 μM, 1 μM, 10 μM and 100 μM nicotine, respectively. (E): Bar graph summarizes the changes in peak frequency of γ oscillations before and after application of various concentrations of nicotine. Gray bars: Control peak frequency (KA alone), Black bars: The peak frequency after application of various concentrations of nicotine (*p < 0.05, **p < 0.01, compared with control, one way RM ANOVA).
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f1: The effects of nicotine on γ oscillations.(A1–C1) KA-induced γ oscillation. (A1): Representative traces of extracellular recordings in hippocampal CA3 before and after KA application; The 1-second waveforms were taken from the steady states before and after application of KA. (B1): The power spectra of the field potentials before and after application of KA; (C1): The time course shows the changes of γ power before and after application of KA. (A2–A5) Representative extracellular recordings of field potentials before and after application of nicotine at 0.25 μM (A2), 1 μM (A3), 10 μM (A4) and 100 μM (A5). (B2–B5) Power spectra of field potentials before and after application of nicotine at 0.25 μM (B2), 1 μM (B3), 10 μM (B4) and 100 μM (B5); (C2–C5) The time courses showing the changes of γ power before and after application of nicotine at 0.25 μM (C2); 1 μM (C3), 10 μM (C4) and 100 μM (C5). (D): Bar graph summarizes the percent changes in γ power before and after application of various concentrations of nicotine. Gray bar: Normalized γ power in control (100%, KA alone). Black bars: The percent changes in γ powers after application of various concentrations of nicotine. *p < 0.05, **p < 0.01, ***p < 0.001, compared with control, one way RM ANOVA, n = 9, 13, 10, 10 for 0.25 μM, 1 μM, 10 μM and 100 μM nicotine, respectively. (E): Bar graph summarizes the changes in peak frequency of γ oscillations before and after application of various concentrations of nicotine. Gray bars: Control peak frequency (KA alone), Black bars: The peak frequency after application of various concentrations of nicotine (*p < 0.05, **p < 0.01, compared with control, one way RM ANOVA).

Mentions: Kainate (KA, 200 nM) induced persistent γ oscillation (20–60 Hz) in rat hippocampal CA3 area. γ oscillation usually takes approximately 1 to 2 hours to achieve steady-state and would last for at least three hours (Fig. 1A1, B1, C1), which is in agreement with previous studies353637. γ oscillations can be blocked by the AMPA/kainate receptor antagonist, NBQX (20 μM), or the GABAA receptor antagonist, bicuculline (20 μM) (n = 5, data not shown), confirming that these oscillations are mediated by excitatory and inhibitory neurotransmission.


The modulation of nicotinic acetylcholine receptors on the neuronal network oscillations in rat hippocampal CA3 area.

Wang Y, Wang Z, Wang J, Wang Y, Henderson Z, Wang X, Zhang X, Song J, Lu C - Sci Rep (2015)

The effects of nicotine on γ oscillations.(A1–C1) KA-induced γ oscillation. (A1): Representative traces of extracellular recordings in hippocampal CA3 before and after KA application; The 1-second waveforms were taken from the steady states before and after application of KA. (B1): The power spectra of the field potentials before and after application of KA; (C1): The time course shows the changes of γ power before and after application of KA. (A2–A5) Representative extracellular recordings of field potentials before and after application of nicotine at 0.25 μM (A2), 1 μM (A3), 10 μM (A4) and 100 μM (A5). (B2–B5) Power spectra of field potentials before and after application of nicotine at 0.25 μM (B2), 1 μM (B3), 10 μM (B4) and 100 μM (B5); (C2–C5) The time courses showing the changes of γ power before and after application of nicotine at 0.25 μM (C2); 1 μM (C3), 10 μM (C4) and 100 μM (C5). (D): Bar graph summarizes the percent changes in γ power before and after application of various concentrations of nicotine. Gray bar: Normalized γ power in control (100%, KA alone). Black bars: The percent changes in γ powers after application of various concentrations of nicotine. *p < 0.05, **p < 0.01, ***p < 0.001, compared with control, one way RM ANOVA, n = 9, 13, 10, 10 for 0.25 μM, 1 μM, 10 μM and 100 μM nicotine, respectively. (E): Bar graph summarizes the changes in peak frequency of γ oscillations before and after application of various concentrations of nicotine. Gray bars: Control peak frequency (KA alone), Black bars: The peak frequency after application of various concentrations of nicotine (*p < 0.05, **p < 0.01, compared with control, one way RM ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4374140&req=5

f1: The effects of nicotine on γ oscillations.(A1–C1) KA-induced γ oscillation. (A1): Representative traces of extracellular recordings in hippocampal CA3 before and after KA application; The 1-second waveforms were taken from the steady states before and after application of KA. (B1): The power spectra of the field potentials before and after application of KA; (C1): The time course shows the changes of γ power before and after application of KA. (A2–A5) Representative extracellular recordings of field potentials before and after application of nicotine at 0.25 μM (A2), 1 μM (A3), 10 μM (A4) and 100 μM (A5). (B2–B5) Power spectra of field potentials before and after application of nicotine at 0.25 μM (B2), 1 μM (B3), 10 μM (B4) and 100 μM (B5); (C2–C5) The time courses showing the changes of γ power before and after application of nicotine at 0.25 μM (C2); 1 μM (C3), 10 μM (C4) and 100 μM (C5). (D): Bar graph summarizes the percent changes in γ power before and after application of various concentrations of nicotine. Gray bar: Normalized γ power in control (100%, KA alone). Black bars: The percent changes in γ powers after application of various concentrations of nicotine. *p < 0.05, **p < 0.01, ***p < 0.001, compared with control, one way RM ANOVA, n = 9, 13, 10, 10 for 0.25 μM, 1 μM, 10 μM and 100 μM nicotine, respectively. (E): Bar graph summarizes the changes in peak frequency of γ oscillations before and after application of various concentrations of nicotine. Gray bars: Control peak frequency (KA alone), Black bars: The peak frequency after application of various concentrations of nicotine (*p < 0.05, **p < 0.01, compared with control, one way RM ANOVA).
Mentions: Kainate (KA, 200 nM) induced persistent γ oscillation (20–60 Hz) in rat hippocampal CA3 area. γ oscillation usually takes approximately 1 to 2 hours to achieve steady-state and would last for at least three hours (Fig. 1A1, B1, C1), which is in agreement with previous studies353637. γ oscillations can be blocked by the AMPA/kainate receptor antagonist, NBQX (20 μM), or the GABAA receptor antagonist, bicuculline (20 μM) (n = 5, data not shown), confirming that these oscillations are mediated by excitatory and inhibitory neurotransmission.

Bottom Line: Nicotine enhanced γ oscillation at concentrations of 0.1-10 μM, but reduced it at a higher concentration of 100 μM.However, these nAChR antagonists failed to block the suppressing role of nicotine on γ.Furthermore, we found that the NMDA receptor antagonist D-AP5 completely blocked the effect of nicotine.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory for the Brain Research of Henan Province, Xinxiang Medical University, Henan Province, Henan PR. China.

ABSTRACT
γ oscillations are associated with higher brain functions such as memory, perception and consciousness. Disruption of γ oscillations occur in various neuro-psychological disorders such as schizophrenia. Nicotinic acetylcholine receptors (nAChR) are highly expressed in the hippocampus, however, little is known about the role on hippocampal persistent γ oscillation. This study examined the effects of nicotine and selective nAChR agonists and antagonists on kainate-induced persistent γ oscillation in rat hippocampal slices. Nicotine enhanced γ oscillation at concentrations of 0.1-10 μM, but reduced it at a higher concentration of 100 μM. The enhancement on γ oscillation can be best mimicked by co-application of α4β2- and α7-nAChR agonist and reduced by a combination of nAChR antagonists, DhβE and MLA. However, these nAChR antagonists failed to block the suppressing role of nicotine on γ. Furthermore, we found that the NMDA receptor antagonist D-AP5 completely blocked the effect of nicotine. These results demonstrate that nicotine modulates γ oscillations via α7 and α4β2 nAChR as well as NMDA activation, suggesting that nAChR activation may have a therapeutic role for the clinical disorder such as schizophrenia, which is known to have impaired γ oscillation and hypo-NMDA receptor function.

No MeSH data available.


Related in: MedlinePlus