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

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.

Multiple Kinases Involved in the Nicotinic Modulation of Gamma Oscillations in the Rat Hippocampal CA3 Area

“…The nicotinic γ oscillation enhancement may be related to the activation of NMDAR and subsequent calcium influx, as D-AP5, in line with previous observations (Wang et al, 2015), completely blocked the effects of nicotine. Calcium influx through the NMDAR is the start of many signaling pathways that alter neuronal and network functions (Perkel et al, 1993; Sobczyk and Svoboda, 2007).…”

Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice

“…81 A neurology system with both A.C.PREAMP NL104 and NL106 AC/DC amplifier (Digitimer) was employed for extracellular field recordings, which were conducted using glass microelectrodes containing ACSF (resistance 2-5 MU). The ACSF contained (in mM) 126 NaCl, 3 KCl, 1.25 NaH2PO 4 , 24 NaHCO 3 , 2 MgSO 4 , 2 CaCl 2 , and 10 glucose.…”

An acetylcholine alpha7 positive allosteric modulator rescues a schizophrenia-associated brain endophenotype in the 15q13.3 microdeletion, encompassing CHRNA7

“…Interestingly, gamma activity after auditory stimulus and the amplitude of auditoryevoked potentials are reduced in 15q13.3 mice, reminiscent of schizophrenia patients (Fejgin et al, 2014), and bringing to attention the fact that resting-state and task-evoked gamma activity might reflect different mechanisms. stimulation can increase gamma oscillations in the hippocampus (Wang et al, 2015) and is also effective in restoring auditory gating deficits characteristic of schizophrenia and 15q13.3 deletion model (Hajos and Rogers, 2010).…”