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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 selective nAChR agonists on γ oscillations.(A1–A3) Representative extracellular recordings of KA-induced field potentials before and after application of α7 nAChR agonist PNU282987 (PNU, 1 μM) (A1), α4β2 nAChR agonist RJR2403 (RJR, 1 μM) (A2) and PNU + RJR (A3). The 1-second waveforms were taken from the steady states under various conditions. (B1–B3) The power spectra of KA-induced field potentials before and after applications of PNU (B1), RJR (B2) and PNU + RJR (B3). (C1–C3) The time course shows the changes in γ power before and after application of PNU (C1), RJR (C2) and PNU + RJR (C3). (D): Bar graph shows the effects of PNU, RJR or PNU + RJR on γ power. Gray bars: Normalized γ power in control (100%, KA alone), Black bars: percent changes in γ powers after application of PNU (n = 10), RJR (n = 9) or PNU + RJR (n = 8). **p < 0.01, compared with control, one way RM ANOVA. The dashed horizontal line located at the top of the graph D indicates the level of percentage change on γ oscillations induced by nicotine (1 μM) alone.
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f2: The effects of selective nAChR agonists on γ oscillations.(A1–A3) Representative extracellular recordings of KA-induced field potentials before and after application of α7 nAChR agonist PNU282987 (PNU, 1 μM) (A1), α4β2 nAChR agonist RJR2403 (RJR, 1 μM) (A2) and PNU + RJR (A3). The 1-second waveforms were taken from the steady states under various conditions. (B1–B3) The power spectra of KA-induced field potentials before and after applications of PNU (B1), RJR (B2) and PNU + RJR (B3). (C1–C3) The time course shows the changes in γ power before and after application of PNU (C1), RJR (C2) and PNU + RJR (C3). (D): Bar graph shows the effects of PNU, RJR or PNU + RJR on γ power. Gray bars: Normalized γ power in control (100%, KA alone), Black bars: percent changes in γ powers after application of PNU (n = 10), RJR (n = 9) or PNU + RJR (n = 8). **p < 0.01, compared with control, one way RM ANOVA. The dashed horizontal line located at the top of the graph D indicates the level of percentage change on γ oscillations induced by nicotine (1 μM) alone.

Mentions: To determine which nAChR subunits play a role on γ enhancement of nicotine, we further tested the effects of the selective α7 nAChR agonist PNU282987 or the α4β2 nAChR agonist RJR2403 alone or in the combination on γ oscillations. Application of PNU282987 (1 μM) or RJR2403 (1 μM) alone enhanced γ oscillation as shown in Fig. 2A1–C1, A2–C2 by representative experiments. The combination of two agonists dramatically enhanced γ power (Fig. 2A3–C3). On average, the percent increase in γ-power was 28 ± 9%, 25 ± 6%, and 61 ± 13% for PNU282987 (n = 10), RJR2403 (n = 9) and PNU282987 + RJR2403 (n = 8), respectively. Compared with control, these changes are all of statistical significance (*p < 0.01, one way RM ANOVA, Fig. 2D).


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 selective nAChR agonists on γ oscillations.(A1–A3) Representative extracellular recordings of KA-induced field potentials before and after application of α7 nAChR agonist PNU282987 (PNU, 1 μM) (A1), α4β2 nAChR agonist RJR2403 (RJR, 1 μM) (A2) and PNU + RJR (A3). The 1-second waveforms were taken from the steady states under various conditions. (B1–B3) The power spectra of KA-induced field potentials before and after applications of PNU (B1), RJR (B2) and PNU + RJR (B3). (C1–C3) The time course shows the changes in γ power before and after application of PNU (C1), RJR (C2) and PNU + RJR (C3). (D): Bar graph shows the effects of PNU, RJR or PNU + RJR on γ power. Gray bars: Normalized γ power in control (100%, KA alone), Black bars: percent changes in γ powers after application of PNU (n = 10), RJR (n = 9) or PNU + RJR (n = 8). **p < 0.01, compared with control, one way RM ANOVA. The dashed horizontal line located at the top of the graph D indicates the level of percentage change on γ oscillations induced by nicotine (1 μM) alone.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: The effects of selective nAChR agonists on γ oscillations.(A1–A3) Representative extracellular recordings of KA-induced field potentials before and after application of α7 nAChR agonist PNU282987 (PNU, 1 μM) (A1), α4β2 nAChR agonist RJR2403 (RJR, 1 μM) (A2) and PNU + RJR (A3). The 1-second waveforms were taken from the steady states under various conditions. (B1–B3) The power spectra of KA-induced field potentials before and after applications of PNU (B1), RJR (B2) and PNU + RJR (B3). (C1–C3) The time course shows the changes in γ power before and after application of PNU (C1), RJR (C2) and PNU + RJR (C3). (D): Bar graph shows the effects of PNU, RJR or PNU + RJR on γ power. Gray bars: Normalized γ power in control (100%, KA alone), Black bars: percent changes in γ powers after application of PNU (n = 10), RJR (n = 9) or PNU + RJR (n = 8). **p < 0.01, compared with control, one way RM ANOVA. The dashed horizontal line located at the top of the graph D indicates the level of percentage change on γ oscillations induced by nicotine (1 μM) alone.
Mentions: To determine which nAChR subunits play a role on γ enhancement of nicotine, we further tested the effects of the selective α7 nAChR agonist PNU282987 or the α4β2 nAChR agonist RJR2403 alone or in the combination on γ oscillations. Application of PNU282987 (1 μM) or RJR2403 (1 μM) alone enhanced γ oscillation as shown in Fig. 2A1–C1, A2–C2 by representative experiments. The combination of two agonists dramatically enhanced γ power (Fig. 2A3–C3). On average, the percent increase in γ-power was 28 ± 9%, 25 ± 6%, and 61 ± 13% for PNU282987 (n = 10), RJR2403 (n = 9) and PNU282987 + RJR2403 (n = 8), respectively. Compared with control, these changes are all of statistical significance (*p < 0.01, one way RM ANOVA, Fig. 2D).

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