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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 antagonists on nicotine's role on γ oscillations.(A1): Representative extracellular recordings in the presence of MLA (200 nM), MLA + KA (200 nM) and MLA + KA + NIC (1 μM). The 1-second waveforms were taken from the steady states under various conditions. (B1): The power spectra of field potentials corresponding to the conditions shown in A1. (C1): The time course shows the changes in γ power before and after application of NIC in the presence of MLA. (A2): Representative extracellular recordings in the presence of DhβE (200 nM), DhβE + KA and DhβE + KA + NIC. (B2): The power spectra of field potentials corresponding to the conditions shown in A2. (C2): The time course shows the changes in γ power before and after application of NIC in the presence of DhβE. (A3): Representative extracellular recordings in the presence of DhβE + MLA, DhβE + MLA + KA and DhβE + MLA + KA + NIC. (B3): The power spectra of field potentials corresponding to the conditions shown in A3. (C3): The time course shows the changes in γ power before and after application of NIC in the presence of DhβE + MLA. (D). The bar graph summarizes the percent changes in γ power before and after application of nicotine in the presence of various nAChR antagonists. Gray bars: Normalized control γ powers for MLA + KA, DhβE + KA or DhβE + MLA + KA; Black bars: percent changes in γ powers after application of nicotine in the presence of MLA + KA, DhβE + KA or DhβE + MLA + KA (**p < 0.01, compared with their own controls, one-way RM ANOVA). (E): Bar graph summarizes the changes in peak frequency in γ oscillations before and after application of nicotine in the presence of nAChR antagonists alone or combined. Gray bars: The peak frequencies before application of nicotine in the presence of MLA + KA, DhβE + KA or DhβE + MLA + KA. Black bars: The peak frequencies after application of nicotine in the presence of MLA + KA, DhβE + KA or DhβE + MLA + KA (*p < 0.05, one-way RM ANOVA).
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f3: The effects of selective nAChR antagonists on nicotine's role on γ oscillations.(A1): Representative extracellular recordings in the presence of MLA (200 nM), MLA + KA (200 nM) and MLA + KA + NIC (1 μM). The 1-second waveforms were taken from the steady states under various conditions. (B1): The power spectra of field potentials corresponding to the conditions shown in A1. (C1): The time course shows the changes in γ power before and after application of NIC in the presence of MLA. (A2): Representative extracellular recordings in the presence of DhβE (200 nM), DhβE + KA and DhβE + KA + NIC. (B2): The power spectra of field potentials corresponding to the conditions shown in A2. (C2): The time course shows the changes in γ power before and after application of NIC in the presence of DhβE. (A3): Representative extracellular recordings in the presence of DhβE + MLA, DhβE + MLA + KA and DhβE + MLA + KA + NIC. (B3): The power spectra of field potentials corresponding to the conditions shown in A3. (C3): The time course shows the changes in γ power before and after application of NIC in the presence of DhβE + MLA. (D). The bar graph summarizes the percent changes in γ power before and after application of nicotine in the presence of various nAChR antagonists. Gray bars: Normalized control γ powers for MLA + KA, DhβE + KA or DhβE + MLA + KA; Black bars: percent changes in γ powers after application of nicotine in the presence of MLA + KA, DhβE + KA or DhβE + MLA + KA (**p < 0.01, compared with their own controls, one-way RM ANOVA). (E): Bar graph summarizes the changes in peak frequency in γ oscillations before and after application of nicotine in the presence of nAChR antagonists alone or combined. Gray bars: The peak frequencies before application of nicotine in the presence of MLA + KA, DhβE + KA or DhβE + MLA + KA. Black bars: The peak frequencies after application of nicotine in the presence of MLA + KA, DhβE + KA or DhβE + MLA + KA (*p < 0.05, one-way RM ANOVA).

Mentions: After the steady state of γ oscillations was reached in the presence of these nAChR antagonists, nicotine (1 μM) was applied. Our results showed that MLA (Fig. 3A1–C1) or DhβE (Fig. 3A2–C2) partially reduced nicotinic enhancement on γ power, but a combination of both antagonists blocked the nicotinic effect (Fig. 3A3–C3). On average, nicotine caused 40 ± 11% (*p < 0.05, one way RM ANOVA, n = 6), 33 ± 10% (*p < 0.05, n = 6) and 1 ± 3% (p > 0.05, n = 7) increase in γ power for the pretreatment of MLA, DhβE and MLA + DhβE, respectively (Fig. 3D). Two way RM ANOVA also revealed that there was a significant interaction between nAChR antagonists and nicotine for the pretreatment of MLA + DhβE (*p < 0.01) and DhβE (*p < 0.05) but not for MLA (p > 0.05). These results indicate that MLA + DhβE pretreatment effectively blocks nicotine-induced increase in γ power.


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 antagonists on nicotine's role on γ oscillations.(A1): Representative extracellular recordings in the presence of MLA (200 nM), MLA + KA (200 nM) and MLA + KA + NIC (1 μM). The 1-second waveforms were taken from the steady states under various conditions. (B1): The power spectra of field potentials corresponding to the conditions shown in A1. (C1): The time course shows the changes in γ power before and after application of NIC in the presence of MLA. (A2): Representative extracellular recordings in the presence of DhβE (200 nM), DhβE + KA and DhβE + KA + NIC. (B2): The power spectra of field potentials corresponding to the conditions shown in A2. (C2): The time course shows the changes in γ power before and after application of NIC in the presence of DhβE. (A3): Representative extracellular recordings in the presence of DhβE + MLA, DhβE + MLA + KA and DhβE + MLA + KA + NIC. (B3): The power spectra of field potentials corresponding to the conditions shown in A3. (C3): The time course shows the changes in γ power before and after application of NIC in the presence of DhβE + MLA. (D). The bar graph summarizes the percent changes in γ power before and after application of nicotine in the presence of various nAChR antagonists. Gray bars: Normalized control γ powers for MLA + KA, DhβE + KA or DhβE + MLA + KA; Black bars: percent changes in γ powers after application of nicotine in the presence of MLA + KA, DhβE + KA or DhβE + MLA + KA (**p < 0.01, compared with their own controls, one-way RM ANOVA). (E): Bar graph summarizes the changes in peak frequency in γ oscillations before and after application of nicotine in the presence of nAChR antagonists alone or combined. Gray bars: The peak frequencies before application of nicotine in the presence of MLA + KA, DhβE + KA or DhβE + MLA + KA. Black bars: The peak frequencies after application of nicotine in the presence of MLA + KA, DhβE + KA or DhβE + MLA + KA (*p < 0.05, one-way RM ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
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f3: The effects of selective nAChR antagonists on nicotine's role on γ oscillations.(A1): Representative extracellular recordings in the presence of MLA (200 nM), MLA + KA (200 nM) and MLA + KA + NIC (1 μM). The 1-second waveforms were taken from the steady states under various conditions. (B1): The power spectra of field potentials corresponding to the conditions shown in A1. (C1): The time course shows the changes in γ power before and after application of NIC in the presence of MLA. (A2): Representative extracellular recordings in the presence of DhβE (200 nM), DhβE + KA and DhβE + KA + NIC. (B2): The power spectra of field potentials corresponding to the conditions shown in A2. (C2): The time course shows the changes in γ power before and after application of NIC in the presence of DhβE. (A3): Representative extracellular recordings in the presence of DhβE + MLA, DhβE + MLA + KA and DhβE + MLA + KA + NIC. (B3): The power spectra of field potentials corresponding to the conditions shown in A3. (C3): The time course shows the changes in γ power before and after application of NIC in the presence of DhβE + MLA. (D). The bar graph summarizes the percent changes in γ power before and after application of nicotine in the presence of various nAChR antagonists. Gray bars: Normalized control γ powers for MLA + KA, DhβE + KA or DhβE + MLA + KA; Black bars: percent changes in γ powers after application of nicotine in the presence of MLA + KA, DhβE + KA or DhβE + MLA + KA (**p < 0.01, compared with their own controls, one-way RM ANOVA). (E): Bar graph summarizes the changes in peak frequency in γ oscillations before and after application of nicotine in the presence of nAChR antagonists alone or combined. Gray bars: The peak frequencies before application of nicotine in the presence of MLA + KA, DhβE + KA or DhβE + MLA + KA. Black bars: The peak frequencies after application of nicotine in the presence of MLA + KA, DhβE + KA or DhβE + MLA + KA (*p < 0.05, one-way RM ANOVA).
Mentions: After the steady state of γ oscillations was reached in the presence of these nAChR antagonists, nicotine (1 μM) was applied. Our results showed that MLA (Fig. 3A1–C1) or DhβE (Fig. 3A2–C2) partially reduced nicotinic enhancement on γ power, but a combination of both antagonists blocked the nicotinic effect (Fig. 3A3–C3). On average, nicotine caused 40 ± 11% (*p < 0.05, one way RM ANOVA, n = 6), 33 ± 10% (*p < 0.05, n = 6) and 1 ± 3% (p > 0.05, n = 7) increase in γ power for the pretreatment of MLA, DhβE and MLA + DhβE, respectively (Fig. 3D). Two way RM ANOVA also revealed that there was a significant interaction between nAChR antagonists and nicotine for the pretreatment of MLA + DhβE (*p < 0.01) and DhβE (*p < 0.05) but not for MLA (p > 0.05). These results indicate that MLA + DhβE pretreatment effectively blocks nicotine-induced increase in γ power.

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