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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

NMDA receptor antagonists, D-AP5 blocked the role of nicotine on γ oscillations.(A1–C1) The effects of 10 μM D-AP5 on 1 μM nicotine's role on γ. (A1): Representative extracellular recordings of field potentials in the presence of KA (200 nM) alone, KA + D-AP5 (10 μM) and KA + D-AP5 + NIC (1 μM). (B1): The power spectra of field potentials corresponding to the conditions shown in A1. (C1): Time course shows the changes in γ power before and after application of NIC in the presence of D-AP5. A2-B2: The effects of 10 μM D-AP5 on 10 μM nicotine's role on γ. (A2): Representative extracellular recordings of field potentials in the presence of KA alone, KA + D-AP5 (10 μM) and KA + D-AP5 + NIC (10 μM). (B2): The power spectra of field potentials corresponding to the conditions shown in A2. (A3–B3) The effects of 10 μM AP5 on 100 μM nicotine's role on γ. (A3): Representative extracellular recordings of field potentials in the presence of KA, KA + D-AP5 (10 μM) and KA + D-AP5 + NIC (100 μM). (B3): The power spectra of field potentials corresponding to the conditions shown in A3. (D): The bar graph summarizes the percent changes in γ power before (gray bars) and after various concentrations of nicotine (1–100 μM) in the presence of 10 μM D-AP5. 10 μM D-AP5 had no effect on γ oscillations (shallow dark bars) and the subsequent application of 1 μM nicotine had no significant effect on γ power (n = 17, black bars). 10 μM D-AP5 also blocked the roles of higher concentrations of nicotine (10 μM, n = 12; 100 μM, n = 6) on γ power. (E): The bar graph summarizes the percent changes in γ power before and after various concentrations of nicotine (1–100 μM) in the presence of 1 μM D-AP5. 1 μM D-AP5 had no effect on γ oscillations (shallow dark bars) and the subsequent application of 1 μM nicotine had no significant effect on γ power (n = 8, black bars). Similarly, 1 μM D-AP5 also blocked the roles of nicotine at higher concentrations of 10 μM (n = 8) and 100 μM (n = 8) on γ power.
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f5: NMDA receptor antagonists, D-AP5 blocked the role of nicotine on γ oscillations.(A1–C1) The effects of 10 μM D-AP5 on 1 μM nicotine's role on γ. (A1): Representative extracellular recordings of field potentials in the presence of KA (200 nM) alone, KA + D-AP5 (10 μM) and KA + D-AP5 + NIC (1 μM). (B1): The power spectra of field potentials corresponding to the conditions shown in A1. (C1): Time course shows the changes in γ power before and after application of NIC in the presence of D-AP5. A2-B2: The effects of 10 μM D-AP5 on 10 μM nicotine's role on γ. (A2): Representative extracellular recordings of field potentials in the presence of KA alone, KA + D-AP5 (10 μM) and KA + D-AP5 + NIC (10 μM). (B2): The power spectra of field potentials corresponding to the conditions shown in A2. (A3–B3) The effects of 10 μM AP5 on 100 μM nicotine's role on γ. (A3): Representative extracellular recordings of field potentials in the presence of KA, KA + D-AP5 (10 μM) and KA + D-AP5 + NIC (100 μM). (B3): The power spectra of field potentials corresponding to the conditions shown in A3. (D): The bar graph summarizes the percent changes in γ power before (gray bars) and after various concentrations of nicotine (1–100 μM) in the presence of 10 μM D-AP5. 10 μM D-AP5 had no effect on γ oscillations (shallow dark bars) and the subsequent application of 1 μM nicotine had no significant effect on γ power (n = 17, black bars). 10 μM D-AP5 also blocked the roles of higher concentrations of nicotine (10 μM, n = 12; 100 μM, n = 6) on γ power. (E): The bar graph summarizes the percent changes in γ power before and after various concentrations of nicotine (1–100 μM) in the presence of 1 μM D-AP5. 1 μM D-AP5 had no effect on γ oscillations (shallow dark bars) and the subsequent application of 1 μM nicotine had no significant effect on γ power (n = 8, black bars). Similarly, 1 μM D-AP5 also blocked the roles of nicotine at higher concentrations of 10 μM (n = 8) and 100 μM (n = 8) on γ power.

Mentions: Previous studies indicate that nAChR activation enhanced NMDA receptor function in the hippocampus31 and dorsolateral prefrontal cortex33. We have thus tested whether NMDA receptor activation contributes to the roles of nicotine on γ. When γ oscillations reached a steady state, NMDA receptor antagonist, D-AP5 (10 μM) was perfused for 40 min and no significant change on γ powers was observed, further application of nicotine (1 μM) caused no obvious changes on γ power (Fig. 5A1–C1). On average, the percent changes of γ powers were 100%, 98.8 ± 5.2% and 90.4 ± 7.6% for the control (KA alone), D-AP5 and D-AP5+nicotine, respectively. There was no statistically significant difference in γ powers between control and D-AP5 or D-AP5+nicotine (n = 17, p > 0.05, one way RM ANOVA).


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)

NMDA receptor antagonists, D-AP5 blocked the role of nicotine on γ oscillations.(A1–C1) The effects of 10 μM D-AP5 on 1 μM nicotine's role on γ. (A1): Representative extracellular recordings of field potentials in the presence of KA (200 nM) alone, KA + D-AP5 (10 μM) and KA + D-AP5 + NIC (1 μM). (B1): The power spectra of field potentials corresponding to the conditions shown in A1. (C1): Time course shows the changes in γ power before and after application of NIC in the presence of D-AP5. A2-B2: The effects of 10 μM D-AP5 on 10 μM nicotine's role on γ. (A2): Representative extracellular recordings of field potentials in the presence of KA alone, KA + D-AP5 (10 μM) and KA + D-AP5 + NIC (10 μM). (B2): The power spectra of field potentials corresponding to the conditions shown in A2. (A3–B3) The effects of 10 μM AP5 on 100 μM nicotine's role on γ. (A3): Representative extracellular recordings of field potentials in the presence of KA, KA + D-AP5 (10 μM) and KA + D-AP5 + NIC (100 μM). (B3): The power spectra of field potentials corresponding to the conditions shown in A3. (D): The bar graph summarizes the percent changes in γ power before (gray bars) and after various concentrations of nicotine (1–100 μM) in the presence of 10 μM D-AP5. 10 μM D-AP5 had no effect on γ oscillations (shallow dark bars) and the subsequent application of 1 μM nicotine had no significant effect on γ power (n = 17, black bars). 10 μM D-AP5 also blocked the roles of higher concentrations of nicotine (10 μM, n = 12; 100 μM, n = 6) on γ power. (E): The bar graph summarizes the percent changes in γ power before and after various concentrations of nicotine (1–100 μM) in the presence of 1 μM D-AP5. 1 μM D-AP5 had no effect on γ oscillations (shallow dark bars) and the subsequent application of 1 μM nicotine had no significant effect on γ power (n = 8, black bars). Similarly, 1 μM D-AP5 also blocked the roles of nicotine at higher concentrations of 10 μM (n = 8) and 100 μM (n = 8) on γ power.
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f5: NMDA receptor antagonists, D-AP5 blocked the role of nicotine on γ oscillations.(A1–C1) The effects of 10 μM D-AP5 on 1 μM nicotine's role on γ. (A1): Representative extracellular recordings of field potentials in the presence of KA (200 nM) alone, KA + D-AP5 (10 μM) and KA + D-AP5 + NIC (1 μM). (B1): The power spectra of field potentials corresponding to the conditions shown in A1. (C1): Time course shows the changes in γ power before and after application of NIC in the presence of D-AP5. A2-B2: The effects of 10 μM D-AP5 on 10 μM nicotine's role on γ. (A2): Representative extracellular recordings of field potentials in the presence of KA alone, KA + D-AP5 (10 μM) and KA + D-AP5 + NIC (10 μM). (B2): The power spectra of field potentials corresponding to the conditions shown in A2. (A3–B3) The effects of 10 μM AP5 on 100 μM nicotine's role on γ. (A3): Representative extracellular recordings of field potentials in the presence of KA, KA + D-AP5 (10 μM) and KA + D-AP5 + NIC (100 μM). (B3): The power spectra of field potentials corresponding to the conditions shown in A3. (D): The bar graph summarizes the percent changes in γ power before (gray bars) and after various concentrations of nicotine (1–100 μM) in the presence of 10 μM D-AP5. 10 μM D-AP5 had no effect on γ oscillations (shallow dark bars) and the subsequent application of 1 μM nicotine had no significant effect on γ power (n = 17, black bars). 10 μM D-AP5 also blocked the roles of higher concentrations of nicotine (10 μM, n = 12; 100 μM, n = 6) on γ power. (E): The bar graph summarizes the percent changes in γ power before and after various concentrations of nicotine (1–100 μM) in the presence of 1 μM D-AP5. 1 μM D-AP5 had no effect on γ oscillations (shallow dark bars) and the subsequent application of 1 μM nicotine had no significant effect on γ power (n = 8, black bars). Similarly, 1 μM D-AP5 also blocked the roles of nicotine at higher concentrations of 10 μM (n = 8) and 100 μM (n = 8) on γ power.
Mentions: Previous studies indicate that nAChR activation enhanced NMDA receptor function in the hippocampus31 and dorsolateral prefrontal cortex33. We have thus tested whether NMDA receptor activation contributes to the roles of nicotine on γ. When γ oscillations reached a steady state, NMDA receptor antagonist, D-AP5 (10 μM) was perfused for 40 min and no significant change on γ powers was observed, further application of nicotine (1 μM) caused no obvious changes on γ power (Fig. 5A1–C1). On average, the percent changes of γ powers were 100%, 98.8 ± 5.2% and 90.4 ± 7.6% for the control (KA alone), D-AP5 and D-AP5+nicotine, respectively. There was no statistically significant difference in γ powers between control and D-AP5 or D-AP5+nicotine (n = 17, p > 0.05, one way RM ANOVA).

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