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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 pretreatment of nAChR antagonists on the roles of higher concentrations of nicotine on γ oscillations.(A1): Representative extracellular recordings of field potentials induced by KA (200 nM) in the presence of DhβE (1 μM) + MLA (1 μM) and DhβE + MLA + NIC (10 μM). (B1): The power spectra of field potentials corresponding to the conditions shown in A1. (A2): Representative extracellular recordings of field potentials induced by KA (200 nM) in the presence of DhβE (1 μM) + MLA (1 μM) and DhβE + MLA + NIC (100 μM). (B2): The power spectra of field potentials corresponding to the conditions shown in A2. (A3): Representative extracellular recordings of field potentials induced by KA (200 nM) in the presence of DhβE (10 μM), MLA (10 μM) and DhβE + MLA + NIC (100 μM). (B3): The power spectra of field potentials corresponding to the conditions shown in A3. (C): Bar graph summarizes the percent changes in γ power before and after application of nicotine at10 μM and 100 μM in the pretreatment of DhβE + MLA (1–10 μM for both). Gray bars: The percent changes in γ power in the pretreatment of DhβE + MLA. Black bars: The percent changes in γ power after application of nicotine in the pretreatment of DhβE + MLA (*p < 0.05, **p < 0.01, ***p < 0.001, compared with control, one way RM ANOVA).
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f4: The effects of pretreatment of nAChR antagonists on the roles of higher concentrations of nicotine on γ oscillations.(A1): Representative extracellular recordings of field potentials induced by KA (200 nM) in the presence of DhβE (1 μM) + MLA (1 μM) and DhβE + MLA + NIC (10 μM). (B1): The power spectra of field potentials corresponding to the conditions shown in A1. (A2): Representative extracellular recordings of field potentials induced by KA (200 nM) in the presence of DhβE (1 μM) + MLA (1 μM) and DhβE + MLA + NIC (100 μM). (B2): The power spectra of field potentials corresponding to the conditions shown in A2. (A3): Representative extracellular recordings of field potentials induced by KA (200 nM) in the presence of DhβE (10 μM), MLA (10 μM) and DhβE + MLA + NIC (100 μM). (B3): The power spectra of field potentials corresponding to the conditions shown in A3. (C): Bar graph summarizes the percent changes in γ power before and after application of nicotine at10 μM and 100 μM in the pretreatment of DhβE + MLA (1–10 μM for both). Gray bars: The percent changes in γ power in the pretreatment of DhβE + MLA. Black bars: The percent changes in γ power after application of nicotine in the pretreatment of DhβE + MLA (*p < 0.05, **p < 0.01, ***p < 0.001, compared with control, one way RM ANOVA).

Mentions: We then tested whether the combined antagonists affect the role of nicotine at higher concentrations. In the presence of MLA + DhβE, 10 μM nicotine caused 11.7 ± 2.2% decrease on γ power (*p < 0.05, compared with control, n = 8, Fig. 4A1, B1, C). These results suggest that nAChR antagonists blocked the nicotine-mediated enhancing role on γ and exposed a small, inhibitory effect of 10 μM nicotine on γ oscillation.


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 pretreatment of nAChR antagonists on the roles of higher concentrations of nicotine on γ oscillations.(A1): Representative extracellular recordings of field potentials induced by KA (200 nM) in the presence of DhβE (1 μM) + MLA (1 μM) and DhβE + MLA + NIC (10 μM). (B1): The power spectra of field potentials corresponding to the conditions shown in A1. (A2): Representative extracellular recordings of field potentials induced by KA (200 nM) in the presence of DhβE (1 μM) + MLA (1 μM) and DhβE + MLA + NIC (100 μM). (B2): The power spectra of field potentials corresponding to the conditions shown in A2. (A3): Representative extracellular recordings of field potentials induced by KA (200 nM) in the presence of DhβE (10 μM), MLA (10 μM) and DhβE + MLA + NIC (100 μM). (B3): The power spectra of field potentials corresponding to the conditions shown in A3. (C): Bar graph summarizes the percent changes in γ power before and after application of nicotine at10 μM and 100 μM in the pretreatment of DhβE + MLA (1–10 μM for both). Gray bars: The percent changes in γ power in the pretreatment of DhβE + MLA. Black bars: The percent changes in γ power after application of nicotine in the pretreatment of DhβE + MLA (*p < 0.05, **p < 0.01, ***p < 0.001, 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

f4: The effects of pretreatment of nAChR antagonists on the roles of higher concentrations of nicotine on γ oscillations.(A1): Representative extracellular recordings of field potentials induced by KA (200 nM) in the presence of DhβE (1 μM) + MLA (1 μM) and DhβE + MLA + NIC (10 μM). (B1): The power spectra of field potentials corresponding to the conditions shown in A1. (A2): Representative extracellular recordings of field potentials induced by KA (200 nM) in the presence of DhβE (1 μM) + MLA (1 μM) and DhβE + MLA + NIC (100 μM). (B2): The power spectra of field potentials corresponding to the conditions shown in A2. (A3): Representative extracellular recordings of field potentials induced by KA (200 nM) in the presence of DhβE (10 μM), MLA (10 μM) and DhβE + MLA + NIC (100 μM). (B3): The power spectra of field potentials corresponding to the conditions shown in A3. (C): Bar graph summarizes the percent changes in γ power before and after application of nicotine at10 μM and 100 μM in the pretreatment of DhβE + MLA (1–10 μM for both). Gray bars: The percent changes in γ power in the pretreatment of DhβE + MLA. Black bars: The percent changes in γ power after application of nicotine in the pretreatment of DhβE + MLA (*p < 0.05, **p < 0.01, ***p < 0.001, compared with control, one way RM ANOVA).
Mentions: We then tested whether the combined antagonists affect the role of nicotine at higher concentrations. In the presence of MLA + DhβE, 10 μM nicotine caused 11.7 ± 2.2% decrease on γ power (*p < 0.05, compared with control, n = 8, Fig. 4A1, B1, C). These results suggest that nAChR antagonists blocked the nicotine-mediated enhancing role on γ and exposed a small, inhibitory effect of 10 μM nicotine on γ oscillation.

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